EXPRESSION OF GAP JUNCTION PROTEINS CONNEXIN-26 AND CONNEXIN-43 IN NORMAL HUMAN BREAST AND IN BREAST-TUMORS

Gap junctional intercellular communication (GJIC) has been proposed as a cellular mechanism for tumour suppression and there is experimental evidence in support of this. If aberrant GJIC contributes to the form ation of human breast tumours, one might expect that the connexins (ga p junction proteins) expressed by epithelial cells in normal human bre ast would be down-regulated in tumour epithelial cells, or that tumour cells might show aberrant expression of other connexin family members . This study examines the immunocytochemical expression of connexins 2 6 (Cx26) and 43 (Cx43) in normal human breast, 11 benign breast lesion s, two special-type carcinomas, and 27 invasive carcinomas of no speci al histological type (NST). Cx26 generally was not expressed at detect able levels in normal human breast, but punctate Cx43 immunostaining o f the myoepithelial cells was found. Cx43 staining of the myoepitheliu m was also a feature of the benign lesions and ductal carcinoma in sit s (DCIS). In general, the epithelial cells of benign lesions failed to stain for either connexin. Similarly, a lobular carcinoma did not exp ress Cx26 or Cx43, but there was punctate Cx43 in the epithelial cells of a mucoid carcinoma. Cx26 was up-regulated in the carcinoma cells o f 15 of the 27 invasive NST carcinomas, although the staining was usua lly cytoplasmic and heterogeneous. Cx43 was expressed by stromal cells , possibly myofibroblasts, in all NST carcinomas. Furthermore, there w as heterogeneous Cx43 expression in the carcinoma cells of 14 of the 2 7 NST carcinomas and the staining was often intercellular and punctate , characteristic of functional connexins. Up-regulation of Cx26 and/or Cx43 in the carcinoma cells of over two-thirds of invasive lesions of NST is not necessarily inconsistent with a tumour suppressor role for GJIC. However, the role of gap junctions in the formation and progres sion of solid human tumours is likely to be more complex than indicate d from experimental systems. (C) 1998 John Wiley & Sons, Ltd.