Journal of Histochemistry and Cytochemistry Priciples for Free Access to Science
  Search:   
    >> Advanced Search

Guidelines | Subscriptions | About | exPRESS - Current - Archive | Business Information | Contact

Originally published as JHC exPRESS on October 18, 2005.
doi:10.1369/jhc.5A6672.2005
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jhc.5A6672.2005v1
54/2/223    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Young, L.
Right arrow Articles by Dong, Q.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Young, L.
Right arrow Articles by Dong, Q.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Journal of Histochemistry and Cytochemistry
Volume 54 (2): 223-229, 2006
Copyright ©The Histochemical Society, Inc.

Ornithine Decarboxylase (ODC) Expression Pattern in Human Prostate Tissues and ODC Transgenic Mice

Lei Young, Robert Salomon, Wendy Au, Charles Allan, Peter Russell and Qihan Dong

Department of Medicine (LY,RS,QD) and Department of Pathology (PR), University of Sydney, Sydney, Australia; Westmead Millennium Institute, Westmead, Australia (WA); ANZAC Research Institute, Concord, Australia (CA); and Department of Anatomical Pathology, Royal Prince Alfred Hospital, Sydney, Australia (PR)

Correspondence to: Lei Young, Rm. 371, Blackburn Bld. D06, Western Ave., University of Sydney, NSW 2006, Australia. E-mail: lyoung{at}ozex.biz


   Summary
Top
 Summary
Introduction
 Materials and Methods
 Results
 Discussion
 Literature Cited
 
Ornithine decarboxylase (ODC) is the key enzyme in the polyamine synthesis pathway and is overexpressed in a variety of cancers. We have performed a detailed immunostaining analysis of the expression of ODC in normal, benign prostatic hyperplasia (BPH), and cancerous prostate tissues. We conclude that ODC is overexpressed in both BPH and neoplastic tissues and that ODC overexpression appears to be an early event in prostate carcinogenesis. The extent of overexpression decreases as cancer progresses. Interestingly, ODC overexpression was also detected in patients who underwent androgen ablation therapy, suggesting ODC overexpression may contribute to the androgen-independent survival of prostate cancer cells. ODC is perinuclear localized in BPH samples but is diffusely cytoplasmic in cancer samples. Having shown ODC overexpression in human prostate cancer, we developed prostate-specific ODC transgenic mice to further investigate whether ODC overexpression alone is a causal factor in prostate carcinogenesis. RT-PCR and immunostaining confirmed that ODC was overexpressed in a subset of prostate epithelial cells. Although minor nucleoli enlargements in some tissues were detected, gross morphological changes were not observed in transgenic prostates. Therefore, overexpression of ODC alone in this subset of prostate epithelial cells is not sufficient to induce prostate carcinogenesis. (J Histochem Cytochem 54:223–229, 2006)

Key Words: prostate cancer • benign prostatic hyperplasia • ornithine decarboxylase • immunostaining • transgenic


   Introduction
Top
 Summary
 Introduction
Materials and Methods
 Results
 Discussion
 Literature Cited
 
ORNITHINE DECARBOXYLASE (ODC) is the key enzyme in polyamine biosynthesis. Activation of ODC and consequently increased concentrations of polyamines are related to tumor promotion and progression (Pegg 1988Go; Tabib and Bachrach 1999Go). Convincing evidence has confirmed the role of ODC in chemical carcinogenesis of mouse skin. ODC expression was induced by a broad range of tumor promoters in mouse skin, and tumor formation can be reduced or blocked by the irreversible inhibitor of ODC, {alpha}-difluoromethylornithine (DFMO) (O'Brien et al. 1997Go; Soler et al. 1998Go; Megosh et al. 2002Go). A link between polyamine levels and tumor grade and stage was also established in colorectal adenocarcinomas (Weiss et al. 2002Go; Hu et al. 2005Go). Elevated levels of ODC have also been found in pancreatic cancer (Subhi et al. 2004Go).

However, although it is clear that ODC overexpression is associated with cancer development, a definitive causal role of ODC overexpression in carcinogenesis has only been shown in NIH/3T3 fibroblast cells (Moshier et al. 1993Go). In transgenic ODC mice, only a promotive role can be shown in the skin after 7,12-dimethylbenzanthracene (DMBA) treatment (Megosh et al. 1995Go; Chen et al. 2000Go).

ODC activity is also increased in prostatic cancer tissues and their respective secretory fluids (Mohan et al. 1999; Bettuzzi et al. 2000; Rhodes et al. 2002Go). Furthermore, in the widely used transgenic mouse model of prostatic cancer (TRAMP), ODC activity is high in cancer tissues, and DFMO treatment resulted in a significant decrease in tumor incidence, volume, and distant metastasis (Gupta et al. 2000Go). Despite this, a detailed study comparing the expression patterns of ODC at the cellular level in benign prostatic hyperplasia (BPH) and prostate cancer tissues has not been conducted. Furthermore, it has not been established whether overexpression of ODC is involved in the initiation or promotion of prostatic carcinogenesis. To address these issues, we first conducted a detailed immunohistochemical (IHC) comparison between normal, BPH, prostatic intraepithelial neoplasia (PIN), and prostatic cancer tissues. This revealed distinct expression patterns and confirmed overexpression of ODC in prostatic cancer tissues. Based on the expression pattern obtained from our IHC studies, we developed a mouse model that specifically expressed the ODC transgene in the prostatic epithelial cells by placing the human ODC gene under the control of the minimal promoter of the rat Probasin gene (Pb). Although no specific phenotype has been observed in these mice, involvement of ODC during carcinogenesis cannot be ruled out because consistent overexpression was not achieved in the transgenic mouse prostate.


   Materials and Methods
Top
 Summary
 Introduction
 Materials and Methods
Results
 Discussion
 Literature Cited
 
Patients and Specimens
Normal organ donor human prostatic tissues were obtained from the New South Wales (NSW) Red Cross. BPH and prostate cancer biopsy tissues were obtained from the Royal Prince Alfred Hospital (RPAH), Sydney, Australia). Whole organ donor prostate glands were dissected by a urological surgeon into transitional/central and peripheral zones using urethra and ejaculatory ducts as landmarks. The study was approved by the RPAH Human Ethics Committee. Paired ventral mouse prostates were collected from Ketalar-overdosed mice via surgical exploration of the abdominal cavity and dissection. Fresh tissues were fixed in 4% buffered formaldehyde, pH 7, and embedded in paraffin.

IHC on Human Prostatic Tissue
IHC staining was performed on normal (n=7), BPH (n=6), PIN (n=6), and prostatic cancer tissues (n=27). Prostatic cancer tissues could be further separated on the basis of androgen dependence. Cancers were either androgen dependent (n=19) or androgen independent (n=8). The cancers were further classified on the basis of Gleason score as determined by a qualified pathologist.

Tissue slides were antigen retrieved in 500 ml of Tris EDTA (10 mM Tris Base, 1 mM EDTA solution, 0.05% Tween 20, pH 9.0) and microwave treated twice for 10 min each at medium high in a 650-W microwave oven. The mouse anti-human ODC monoclonal antibody (ODC-29, mouse ascites fluid) was obtained from Accurate Chemicals (Westbury, NY), and immunoreactivity was visualized by indirect peroxidase staining with Vectastain ABC kit (Vector Laboratories; Burlingame, CA), following manufacturer's instructions.

Following immunodetection, a pathologist attributed a relative stain intensity to the section. The relative stain intensity could be anywhere from 0 to 3 (3 being the most intense). The relative stain intensity is a measure of difference between the normal and abnormal cells in each section. Therefore, the comparison of ODC levels between cancer and normal, BPH and normal, and PIN and normal was made from tissues found within the one section, thus minimizing the need for inter-patient comparisons.

Transgene Construction and Preparation of Transgenic Mice
Pb promoter (–426 to +28) was PCR amplified from rat genomic DNA with primers containing BamHI and XhoI sites (5'-TGGATCCAGCTTCCACAAGTG CATTT-3' and 5'-TCTCGAGTCTGTAGGTATCTGGACCT-3'). ODC was amplified from human prostate cDNA with primers containing XhoI and NotI sites (5'-ACTCGAGCATGAACAACTTTGGTAATGA-3' and 5'-CGCGGCCGCAAAT CCCTTAATTCAAGCTA-3'). Both Pb and ODC were cloned into pBK-RSV vector (Stratagene; La Jolla, CA) through the intermediate TA cloning vector pGEM-T EASY (Promega; Madison, WI) using standard cloning techniques. Twenty µg of the final vector was digested with BamHI and MluI and microinjected into fertilized C3H mouse oocytes as described previously (Allan et al. 2001Go). DNA from founder mouse toes was extracted, and transgenic mice were confirmed by PCR amplification of the DNA with primers PbF1 (5'-GACACTGCCCATGCCAATCA) and ODCR1 (5'-ACAGCGCTCAACAATCC GATC- 3'). Routine screening of mice was carried out by amplifying toe DNA.

Confirmation of Transgene Expression by RT-PCR
Total RNA was extracted from mouse prostates harvested from heterozygous and non-transgenic mice with Tri-Reagent (Invitrogen; Carlsbad, CA). Two µg of the total RNA were treated with DNase I (Invitrogen) and reverse transcribed with Superscript II reverse transcriptase (Invitrogen). The resulting cDNA (1 µl) was either subjected to 40 cycles PCR with primers ODCVF (5'-TATTACAATTCACTGGCCGTCGTTT-3') and ODCVR (5'-AATGAGCCTTGGG ACTGTGAATCTA-3') for ODC transgene or 30 cycles with primers ACTF (5'-CCGGGACCTGACTGACTACCT-3') and ACTR (5'-GCATTTGCGGTGGACGA-3') for ß-actin.

Confirmation of Transgene Expression by IHC
To confirm overexpression of the ODC transgene at the protein level, IHC was performed on prostate harvested from ODC transgenic mice at 33 weeks (n=2), 24 weeks (n=6), 18 weeks (n=3), and 12 weeks (n=2) of age, together with age-matched wild-type prostates (n=8). The antibody was diluted 1:200 and used in conjunction with the Animal Research Kit (DAKO; Carpinteria, CA) following manufacturer's instructions. All images were taken with Olympus BX51 microscope (Olympus; Tokyo, Japan) under the same conditions. Hematoxylin and eosin staining was performed on the same samples, and the morphology was evaluated by a qualified pathologist without knowing the transgenic status.


   Results
Top
 Summary
 Introduction
 Materials and Methods
 Results
Discussion
 Literature Cited
 
ODC Expression Pattern in Normal, BPH, PIN, and Cancer Tissues
ODC protein expression was examined by IHC in normal, BPH, PIN, and cancer tissues of human prostates (Figure 1 ; Table 1). Cytoplasmic immunoreactivity was detected in the secretory epithelial cells and endothelial cells in normal prostates (n=7) and was distributed evenly within the cells. No expression was detected in basal epithelial cells, fibroblasts, or smooth muscle cells. There was no significant difference between expression patterns of the peripheral zone and transitional/central zone of the normal prostates (Figure 1A). In BPH samples (n=7), strong perinuclear staining was detected mainly at the basal side of the secretory epithelial cells. Compared with adjacent normal tissue, ODC expression in BPH secretory epithelial cells is stronger, and the cellular location is also unique (Figure 1B).



View larger version (121K):
[in this window]
[in a new window]
  		Figure 1

Protein expression pattern of ornithine decarboxylase (ODC) in human prostate. (A) Normal organ donor peripheral zone tissue. (B) Benign prostatic hypertrophic tissue. (C) High-grade prostatic intraepithelial neoplasia tissue. (D) Prostate cancer tissue. (E) Isotype control. Magnification x200.

 

View this table:
[in this window]
[in a new window]
  		Table 1

Ornithine decarboxylase relative intensity in human prostate cancer tissues compared to adjacent normal tissues

 
High-grade PIN has been shown to be linked to prostate cancer (Ashida et al. 2004Go) and is recognized as having a significant predictive value for prostatic cancer. We therefore analyzed ODC expression in PIN from radical prostatectomy patients. As shown in Figure 1C, overexpression (compared with normal tissue) of ODC in the cytoplasm of secretory epithelium for high-grade PIN can be detected in all samples (n=6). Expression in adjacent normal glands is comparable to that in the organ donor prostates. ODC expression in PIN is more diffuse compared with BPH, and expression levels are similar between the two.

All prostate cancer tissue analyzed (with the exception of one specimen) showed an increase in ODC expression between the cancerous and adjacent normal tissue, and immunoreactivity was strongest at the apical side of the epithelial cells (Figure 1D). Although this was true for both androgen-dependent and androgen-ablated sections, ODC expression was markedly higher in the non-androgen-ablated sections. Analysis (Student's t-test) between sections having a relative stain intensity of 1, 2, or 3 showed that there was no statistical correlation between Gleason score and relative stain intensity.

Confirmation of Presence of Transgene mRNA in the Mouse Prostate
To investigate whether ODC overexpression alone can be a causal factor in prostatic cancer, we generated a transgenic ODC mouse line with ODC expression driven by prostate-specific rat Pb promoter. Because mouse and human ODC catalyze the same reaction and show 90% identity in amino acid sequence, human ODC cDNA was used as the transgene. To confirm the presence of transgene-derived ODC mRNA in the prostate, we amplified cDNA with primers specific for the vector sequence section of the transgene so that any amplification detected should have arisen from the transgene. As shown in Figure 2 , ODC mRNA expression was detected only in the heterozygote ODC transgenic mouse prostate, whereas ß-actin quantities remained constant in both transgenic and non-transgenic mouse prostates. This confirms ODC transgene expression in the prostates of transgenic mice at the mRNA level.



View larger version (100K):
[in this window]
[in a new window]
  		Figure 2

RT-PCR analysis showing expression of ODC transgene mRNA in mouse prostate. Lane 1, transgene was expressed in heterozygous mouse prostate; Lane 2, transgene expression was not detected in wild-type mouse prostate; Lane 3, 1 kb plus DNA marker (Invitrogen); Lanes 4 and 5, ß-actin expression in heterozygous and wild-type mouse prostates.

 
Protein Levels of the ODC Transgene in the Mouse Prostate
To evaluate the expression level of ODC protein in the transgenic mouse prostates, we performed IHC staining on the ventral lobes of both transgenic and non-transgenic prostates between 12 and 33 weeks of age. Ventral lobes are selected because previous reports have shown that the minimal Pb promoter is more active in these lobes (Greenberg et al. 1994Go). Because the monoclonal antibody used was of mouse origin, the ARK kit (DAKO) was utilized to avoid nonspecific binding of the secondary antibody to endogenous mouse IgGs. As shown in Figure 3 , the antibody stained epithelial cells exclusively; staining was not detected in the stromal compartment. Within the same transgenic prostate, there were areas with high ODC expression (Figure 3A) and areas where ODC expression was barely detectable (Figure 3B). Similarly, in non-transgenic prostates, there were also areas with moderate (Figure 3C) or no (Figure 3D) ODC expression. However, all 13 transgenic prostates contained areas with ODC expression levels above those detected in the non-transgenic prostates, indicating that ODC overexpression was at least achieved in a subset of cells. No significant difference in expression pattern was observed in prostates of different ages. Tissue sections of the same prostates were also H–E stained and evaluated blindly by a pathologist. Although significant changes in morphology or histology were not detected, nucleoli enlargements were detected in some prostatic cells of the transgenic mice.



View larger version (134K):
[in this window]
[in a new window]
  		Figure 3

ODC protein expression in mouse ventral prostates. (A) ODC transgenic prostates with strong ODC staining. (B) Weak ODC-stained areas in the same prostate as in (A). (C) Relatively strong staining in wild-type mouse prostate. (D) Weak staining in the same prostate as in (C). ODC prostate expression pattern. Magnification x200.

 

   Discussion
Top
 Summary
 Introduction
 Materials and Methods
 Results
 Discussion
Literature Cited
 
In the present work we examined in detail the protein expression pattern of ODC in normal, BPH, and prostatic cancer tissues and clearly revealed overexpression of ODC at protein level in both BPH and cancer samples. Interestingly, apart from the changes at the protein level, BPH samples showed perinuclear localization patterns distinct from normal and cancer samples. In keratinocytes, ODC localization has been shown to correlate with changes in the cytoskeleton network. In normal human epidermal keratinocytes, ODC exhibited perinuclear expression patterns, which became diffusely cytoplasmic after cytoskeleton disruption by TPA, cytochalasin B/D, or DFMO (Pomidor et al. 1995Go). The different localization patterns thus may indicate a more stable cytoskeleton in BPH and disruption of the cytoskeleton in PIN and prostate cancer cells. This difference serves as further evidence that PIN rather than BPH may be the precursor of prostate cancer.

ODC overexpression was detected as early as in PIN, suggesting ODC could be involved in the early stages of the carcinogenesis process and could be involved in promoting the progression of PIN to invasive cancer. Overexpression of ODC can be detected in all cancer tissues examined, and although the staining patterns were heterogeneous, the increase of ODC can be concluded to be an early event in prostate carcinogenesis.

To investigate the role of ODC overexpression in prostatic cancer, we developed a prostate-specific ODC transgenic mouse model. Immunostaining results suggest that ODC was achieved at least in a subset of the prostate epithelial cells. The reason that overexpression of ODC was not achieved in all the prostate epithelial cells may be due to the tight posttranslational regulation of ODC by ODC antizyme (Murakami et al. 1992Go), as the normal transcriptional (promoter and enhancer) regulatory sequences have been replaced by the Pb promoter, and the translational regulatory sequences, the 5' and 3' untranslated regions (UTR) (Manzella et al. 1991Go), have been eliminated in the transgene. Prostate epithelial cells display different ODC regulation levels intrinsically, as heterogeneous ODC expression has also been shown in wild-type prostates in previous studies (Muller et al. 1986Go). Their study has revealed the existence of three types of prostatic epithelial cells displaying high, medium, or low levels of ODC. Therefore, the increased ODC levels detected in some regions of the transgenic mouse prostate may reflect true overexpression in cells that have minimal antizyme regulation (those cells that have high wild-type ODC levels).

Despite that overexpression of ODC was achieved in a subset of the transgenic prostate epithelial cells, cell transformation was not observed, which means that overexpression of ODC alone in this subset of cells could not serve as a causal factor in prostate carcinogenesis. However, a conclusion on the role of ODC in prostate cancer cannot be made without the overexpression of ODC in all of the transgenic prostate epithelial cells, which requires the escape from antizyme regulation. It should be noted that in the only transgenic ODC model that developed skin tumors after chemical carcinogen initiation, the ODC transgene is a C-terminal truncated copy (Megosh et al. 1995Go), which could no longer be degraded by the endogenous antizyme. We have chosen to use the full human ODC gene because in an earlier study the full human ODC including its promoter has been used as the transgene to achieve overexpression in most mouse tissues (Halmekyto et al. 1991Go). We reasoned that because the ODC used was of human origin, it may be able to escape the mouse antizyme control without C-terminal truncation. However, our result indicates this may not be the case. Therefore, in future studies the C-terminal truncated ODC gene should be used instead to achieve more stable overexpression of ODC.


   Footnotes
 
Received for publication February 28, 2005; accepted September 20, 2005


   Literature Cited
Top
 Summary
 Introduction
 Materials and Methods
 Results
 Discussion
 Literature Cited
 

Allan CM, Haywood M, Swaraj S, Spaliviero J, Koch A, Jimenez M, Poutanen M, et al. (2001) A novel transgenic model to characterize the specific effects of follicle-stimulating hormone on gonadal physiology in the absence of luteinizing hormone actions. Endocrinology 142:2213–2220[Abstract/Free Full Text]

Ashida S, Nakagawa H, Katagiri T, Furihata M, Iiizumi M, Anazawa Y, Tsunoda T, et al. (2004) Molecular features of the transition from prostatic intraepithelial neoplasia (PIN) to prostate cancer: genome-wide gene-expression profiles of prostate cancers and PINs. Cancer Res 64:5963–5972[Abstract/Free Full Text]

Bettuzzi S, Davalli P, Astancolle S, Carani C, Madeo B, Tampieri A, Corti A (2000) Tumor progression is accompanied by significant changes in the levels of expression of polyamine metabolism regulatory genes and clusterin (sulfated glycoprotein 2) in human prostate cancer specimens. Cancer Res 60:28–34[Abstract/Free Full Text]

Chen Y, Megosh LC, Gilmour SK, Sawicki JA, O'Brien TG (2000) K6/ODC transgenic mice as a sensitive model for carcinogen identification. Toxicol Lett 116:27–35[CrossRef][Medline]

Greenberg NM, DeMayo FJ, Sheppard PC, Barrios R, Lebovitz R, Finegold M, Angelopoulou R, et al. (1994) The rat probasin gene promoter directs hormonally and developmentally regulated expression of a heterologous gene specifically to the prostate in transgenic mice. Mol Endocrinol 8:230–239[Abstract/Free Full Text]

Gupta S, Ahmad N, Marengo SR, MacLennan GT, Greenberg NM, Mukhtar H (2000) Chemoprevention of prostate carcinogenesis by alpha-difluoromethylornithine in TRAMP mice. Cancer Res 60:5125–5133[Abstract/Free Full Text]

Halmekyto M, Hyttinen JM, Sinervirta R, Utriainen M, Myohanen S, Voipio HM, Wahlfors J, et al. (1991) Transgenic mice aberrantly expressing human ornithine decarboxylase gene. J Biol Chem 266:19746–19751[Abstract/Free Full Text]

Hu HY, Liu XX, Jiang CY, Lu Y, Liu SL, Bian JF, Wang XM, et al. (2005) Ornithine decarboxylase gene is overexpressed in colorectal carcinoma. World J Gastroenterol 11:2244–2248[Medline]

Manzella JM, Rychlik W, Rhoads RE, Hershey JW, Blackshear PJ (1991) Insulin induction of ornithine decarboxylase. Importance of mRNA secondary structure and phosphorylation of eucaryotic initiation factors eIF-4B and eIF-4E. J Biol Chem 266:2383–2389[Abstract/Free Full Text]

Megosh L, Gilmour SK, Rosson D, Soler AP, Blessing M, Sawicki JA, O'Brien TG (1995) Increased frequency of spontaneous skin tumors in transgenic mice which overexpress ornithine decarboxylase. Cancer Res 55:4205–4209[Abstract/Free Full Text]

Megosh LC, Hu J, George K, O'Brien TG (2002) Genetic control of polyamine-dependent susceptibility to skin tumorigenesis. Genomics 79:505–512[CrossRef][Medline]

Mohan RR, Challa A, Gupta S, Bostwick DG, Ahmad N, Agarwal R, Marengo SR, et al. (1999) Overexpression of ornithine decarboxylase in prostate cancer and prostatic fluid in humans. Clin Cancer Res 5:143–147[Abstract/Free Full Text]

Moshier JA, Dosescu J, Skunca M, Luk GD (1993) Transformation of NIH/3T3 cells by ornithine decarboxylase overexpression. Cancer Res 53:2618–2622[Abstract/Free Full Text]

Muller M, Bernstein HG, Pajunen A, Jarvinen M, Dorn A (1986) Immunohistochemical demonstration of ornithine decarboxylase in tissues. A preliminary study. Acta Histochem Suppl 33:197–199[Medline]

Murakami Y, Matsufuji S, Kameji T, Hayashi S, Igarashi K, Tamura T, Tanaka K, et al. (1992) Ornithine decarboxylase is degraded by the 26S proteasome without ubiquitination. Nature 360:597–599[CrossRef][Medline]

O'Brien TG, Megosh LC, Gilliard G, Soler AP (1997) Ornithine decarboxylase overexpression is a sufficient condition for tumor promotion in mouse skin. Cancer Res 57:2630–2637[Abstract/Free Full Text]

Pegg AE (1988) Polyamine metabolism and its importance in neoplastic growth and a target for chemotherapy. Cancer Res 48:759–774[Abstract/Free Full Text]

Pomidor MM, Ruhl KK, Zheng P, Song Y, Janne OA, Tuan RS, Hickok NJ (1995) Relationship between ornithine decarboxylase and cytoskeletal organization in cultured human keratinocytes: cellular responses to phorbol esters, cytochalasins, and alpha-difluoromethylornithine. Exp Cell Res 221:426–437[CrossRef][Medline]

Rhodes DR, Barrette TR, Rubin MA, Ghosh D, Chinnaiyan AM (2002) Meta-analysis of microarrays: interstudy validation of gene expression profiles reveals pathway dysregulation in prostate cancer. Cancer Res 62:4427–4433[Abstract/Free Full Text]

Soler PA, Gilliard G, Megosh L, George K, O'Brien TG (1998) Polyamines regulate expression of the neoplastic phenotype in mouse skin. Cancer Res 58:1654–1659[Abstract/Free Full Text]

Subhi AL, Tang B, Balsara BR, Altomare DA, Testa JR, Cooper HS, Hoffman JP, et al. (2004) Loss of methylthioadenosine phosphorylase and elevated ornithine decarboxylase is common in pancreatic cancer. Clin Cancer Res 10:7290–7296[Abstract/Free Full Text]

Tabib A, Bachrach U (1999) Role of polyamines in mediating malignant transformation and oncogene expression. Int J Biochem Cell Biol 31:1289–1295[CrossRef][Medline]

Weiss TS, Bernhardt G, Buschauer A, Thasler WE, Dolgner D, Zirngibl H, Jauch KW (2002) Polyamine levels of human colorectal adenocarcinomas are correlated with tumor stage and grade. Int J Colorectal Dis 17:381–387[CrossRef][Medline]


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 BioinformaticsHome page
M. Osl, S. Dreiseitl, B. Pfeifer, K. Weinberger, H. Klocker, G. Bartsch, G. Schafer, B. Tilg, A. Graber, and C. Baumgartner
A new rule-based algorithm for identifying metabolic markers in prostate cancer using tandem mass spectrometry
Bioinformatics, December 15, 2008; 24(24): 2908 - 2914.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
S. C. Roberts, Y. Jiang, J. Gasteier, B. Frydman, L. J. Marton, O. Heby, and B. Ullman
Leishmania donovani Polyamine Biosynthetic Enzyme Overproducers as Tools To Investigate the Mode of Action of Cytotoxic Polyamine Analogs
Antimicrob. Agents Chemother., February 1, 2007; 51(2): 438 - 445.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jhc.5A6672.2005v1
54/2/223    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Young, L.
Right arrow Articles by Dong, Q.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Young, L.
Right arrow Articles by Dong, Q.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?


Guidelines | Subscriptions | About | exPRESS - Current - Archive | Business Information | Contact