Endometrial stromal cells regulate gap-junction function in normal human endometrial epithelial cells but not in endometrial carcinoma cells

Gap junctions are transmembrane proteins comprised of six connexin subunits that facilitate direct solute transport between adjacent cells through gap junctions. Previous studies from other laboratories have documented a corr elation between reduced gap-junction function and malignant transformation. In endometrial cancer, a characteristic finding is a reduction in the numb er of stromal cells surrounding the malignant epithelial cells. Thus, the f ocus of this study was to determine the effect of endometrial stromal cells on gap-junction function in normal and malignant endometrial epithelial ce lls. To perform these studies, we evaluated normal endometrial epithelial c ells and human endometrial epithelial cells including FEEC (fetal endometri al epithelial cells immortalized with simian virus 40 large-T antigen), HEC -1A (endometrial carcinoma stage 1A), and RL-95-2 (endometrial carcinoma gr ade II). Cap-junctional intercellutar communication (GJIC) could not be dem onstrated for any of the cell lines. Low levels of GJIC were observed for n ormal epithelial cells and higher levels were found between stromal cells. Increased levels of GJIC were observed between the epithelial cells when th ey were cocultured with stromal cells. The transformed epithelial cells sho wed no GJIC when cultured alone or when in coculture with stromal cells. Th e results suggest that endometrial stromal cells may help to regulate this differentiated function of endometrial epithelial cells and that malignant endometrial epithelial cells are not responsive to these regulatory signals , Mol. Carcinog. 28:70-75, 2000. (C) 2000 Wiley-Liss, Inc.