Modulation of mammary carcinoma cell phenotype and keratin expression patterns by retinoic acid

Immunohistochemical and biochemical procedures were used to study the influence of retinoic acid (RA) on cellular expression and distribution of cytokeratins (CKs) in feline mammary carcinoma cells. These cells were grown in vitro as established cell lines (K248C and K266) and in vivo as xenografts in athymic mice. The results were compared with the distribution of CKs in normal feline mammary gland and in a series of invasive mammary carcinomas previously probed with a panel of monoclonal antibodies specific for individual CKs. Coexpression of CKs of both major mammary gland cell types (myoepithelial cells, MECs, CKs 5/14 positive, and luminal epithelial cells, LECs CKs8/18 positive) by K248C and K266 cells, suggested a stem cell-like character of both cell lines. RA increased CK19 expression in both cell lines and CK19 was also present in tumors developed in nude mice from both RA untreated (CK19 negative) and RA-treated (CK19 positive) K248C and K266 cells. In addition, RA had cell line specific effects as well. RA treatment induced differentiation of K248C cells to more mature LEC-like cells and this change was accompanied by the loss of the MEC keratins CKs 5/14. Under the same culture conditions however, RA treatment did not induce morphological changes in the K266 cell line and the expression of CKs 5/14 was not significantly reduced. These findings suggest that the modulation of CK19 and CKs 5/14 expression observed in mammary carcinoma cells upon RA treatment might be regulated through different pathways.