ODC Expression Pattern in Human Prostate Tissues and ODC Transgenic Mice
Lei Young 1*, Robert Salomon 1, Wendy Au 1, Charles Allan 1, Peter Russell 1 and Qihan Dong 1
1 Department of Medicine, University of Sydney, Australia (LY,RS,QD); Westmead Millennium Institute, Australia (WA); ANZAC Research Institute, Australia (CA); and Department of Anatomical Pathology, Royal Prince Alfred Hospital, and Department of Pathology, University of Sydney, Australia (PR)
* To whom correspondence should be addressed. E-mail: lyoung{at}ozex.biz.
Submitted on February 28, 2005
Accepted on 20 September 2005
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Abstract |
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Ornithine Decarboxylase (ODC) is the key enzyme in the polyamine synthysis pathway, and is found to be overexpressed in a variety of cancers. We have performed a detailed immunostaining analysis of the expression of ODC in normal, benign hyperplastic (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 overexprerssion in human prostate cancer, we developed a 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 the 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.
Key Words:
prostate cancer, BPH, ODC, immunostaining, transgenic