Immunohistochemical Analysis of MUC5B Apomucin Expression in Breast Cancer and Non-malignant Breast Tissues
Cecilia Sóñora 1, Daniel Mazal 1, Nora Berois 1, Marie-Pierre Buisine 1, Luis Ubillos 1, Mario Varangot 1, Enrique Barrios 1, Julio Carzoglio 1, Jean-Pierre Aubert 1 and Eduardo Osinaga 1*
1 Departamento de Bioquímica, Laboratorio de Oncología Básica (CS,DM,NB,LU,EO) and Departamento de Biofísica (EB), Facultad de Medicina, Servicio de Oncología Clínica, Hospital de Clínicas (MV), and Departamento de Anatomía Patológica, Facultad de Odontología (JC), Universidad de la República, Montevideo, Uruguay; and Unité 560 INSERM, 59045 Lille Cedex and University of Lille 2, France (M-PB,J-PA)
* To whom correspondence should be addressed. E-mail: eosinaga{at}fmed.edu.uy.
Submitted on June 19, 2005
Accepted on 1 August 2005
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Abstract |
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A deregulation of several MUC genes (MUC1, MUC2, MUC3, MUC5AC and MUC6) was previously demonstrated in breast carcinomas. Considering that recently we found the "non-mammary" MUC5B mRNA in primary breast tumors (Berois et al. Int. J. Cancer 103:550, 2003), we undertook the present study to evaluate the expression profile of MUC5B protein product in breast tissues, using LUM5B-2 antisera raised against sequences within the nonglycosylated regions of this apomucin. The expression of MUC5B by breast cancer cells was confirmed by immunocytochemistry, in situ hybridization and Western blot on MCF-7 cancer cells. Using an immunohistochemical procedure, MUC5B apomucin was detected in 34/42 (81%) primary breast tumors, in 13/14 (92.8%) samples of nonmalignant breast diseases, in 8/19 (42.1%) samples of normal-appearing breast epithelia adjacent to cancer, and in 0/5 normal control breast samples. The staining pattern of MUC5B was very different when comparing breast cancer cells (cytoplasmic), and nonmalignant breast cells (predominantly apical and in the secretory material). We analyzed MUC5B mRNA expression using RT-PCR in bone marrow aspirates from 22/42 patients with breast cancer, to compare with MUC5B protein expression in the primary tumors. A good correlation was observed, since the 6 MUC5B positive bone marrow samples also displayed MUC5B expression in the tumor. Our results show, for the first time at protein level, that MUC5B apomucin is up-regulated in breast cancer. Its characterization could provide new insights about breast cancer cells glycobiology.
Key Words:
breast cancer, mucin, MUC genes, MUC5B, immunohistochemistry
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