MUC1 protein over-expression is mediated by MUC1 gene amplification in invasive breast carcinoma cells.

CROCE MV; LACUNZA E; BAUDIS M; COLUSSI AG; SEGAL EIRAS A; ABBA MC

Oslo

Congreso; The European Association for Cancer Research (EACR)-21.; 2010

The European Association for Cancer Research (EACR)

The Mucin 1 gene (MUC1), which is located on chromosome region 1q21.3-q22, is aberrantly over-expressed in approximately 90% of human breast cancers. Several studies have shown that MUC1 over-expression is due to transcriptional regulatory events. However, the importance of gene amplification as a mechanism leading to the increase of MUC1 expression in breast cancer has been poorly characterized. The aim of this study was to evaluate the role of MUC1 gene amplification and protein expression in human breast cancer development. Using real-time quantitative PCR (Q-PCR) and immunohistochemistry (IHC) methods, 89 breast tissue samples were analyzed for MUC1 gene amplification and protein expression. Q-PCR analysis showed MUC1 genomic amplification and a positive association with the histopathological group in 12% (1 out of 8) of benign lesions and 38% (23 out of 60) of primary invasive breast carcinoma samples (p=0.004). Array-CGH meta-analysis of 886 primary invasive breast carcinomas obtained from 22 studies showed MUC1 genomic gain in 43.7% (387 out of 886) of the samples. Moreover, we identified highly statistical significant association between MUC1 gene amplification and MUC1 protein expression assessed by IHC and western-blot (p<0.0001). In conclusion, this study demonstrated that MUC1 copy number increases from normal breast tissue to primary invasive breast carcinomas in correlation with MUC1 protein expression.