Deficiency of connexin43 gap junctions is an independent marker for breasttumors

Gap junctions are intercellular channels that are formed From members of a family of proteins, the connexins (Cxs). Gap junctions play an important ro le in vital functions, including the regulation of cell growth and cell dif ferentiation, Here, we examined the expression of Cx43, a major Cx in breas t tissue, in 32 surgical specimens obtained from breast cancer patients who underwent a primary surgical resection prior to chemotherapy or radiothera py treatments. The expression of Cx43 gap junctions was compared to the lev els of estrogen, progesterone, and erbB2 tyrosine kinase receptors. In addi tion, a panel of breast cancer cell lines and a series of normal rat mammar y tissues and rat mammary tumors induced in viva by dimethylbenz(a)anthrace ne were studied, We demonstrated that the lack of Cx43 gap junctions is a c ommon feature of human mammary cancer tissues compared to nonneoplastic: br east tissues surrounding primary tumors. Cx43 gap junctions were not observ ed in ductal carcinomas in situ, infiltrating ductal carcinomas, and infilt rating lobular carcinomas, and they seem to be independent of estrogen, pro gesterone, and erbB2 receptor status. In breast cancer cell lines and roden t mammary carcinoma tissues, down-regulation of Cx43 occurs at the mRNA lev el, suggesting a transcriptional mechanism for the decrease of Cx43 protein in breast cancer. In summary, this study provides evidence of decreased ex pression of Cx43 gap junctions in breast cancer at various stages of progre ssion as well as breast cancer cell lines and raises the possibility that C x43 may be a useful marker for detecting early oncogenesis in the breast, B ecause Cx43 gap junctions are lacking in breast cancer and restoration of C x43 has been shown to reverse the malignant phenotype in vitro, pharmacolog ical up-regulation of Cx43 may prove beneficial in cancer therapeutics.