Different expression of WWOX in estrogen receptor positive and negative breast cancer. Relation to proliferation and apoptosis

Introduction: Breast carcinogenesis depends on sex hormone receptors. Numerous of genes are involved in estrogen signaling pathway as well as in cancer development and progression. Expression deregulation plays important role in switching genes from normal and controlled into carcinogenesis promoting activity. We analyzed correlation between estrogen receptor status of breast cancers and expression of selected genes. Material and Methods: Our study was based on evaluation of panel of 10 genes (Bax, Bcl2, BRCA1, CCND1, CCNE1, CDH1, ERBB2, Ki67, TP73 and WWOX) using real-time RT-PCR in 132 samples of primary breast cancer. Results: Our data revealed correlation between the level of WWOX transcription and estrogen and progesterone status. ER positive tumors had higher expression of WWOX mRNA than ER negative ones. Moreover, tumors ERposPRpos showed several times higher expression of WWOX than ERnegPRneg. We also noticed that there was statistically significant correlation between WWOX transcription level and proliferation in the ER positive tumors. In the same cancer group we found positive correlation between WWOX expression Bcl2 transcription and Bcl2/Bax ratio which is marker of apoptosis. Conclusions: Presented study supports the hypothesis that WWOX is involved in sex hormone signaling and its expression level plays important role in breast carcinogenesis. (Clin. Exp. Med. Lett. 2005; 46(4):25-30)

Keywords: carcinogenesis, tumors suppressor genes, WWOX