Characterization of Integrin Expression in a Well Differentiated Endometrial Adenocarcinoma Cell Line (Ishikawa)1

The pattern of constitutive and cycle-dependent integrins in normal endometrium has recently been established, suggesting a role for cell adhesion molecules in endometrial receptivity and implantation. Currently few, if any, models exist for the study of human endometrial integrins and their role in establishment of the receptive endometrial phenotype. The Ishikawa cell line maintains functional estrogen receptors and progesterone receptors. The progesterone receptors in these cells are inducible by priming with estradiol and down-regulated by treatment with progesterone. In the present study the pattern of integrin expression in this well differentiated endometrial cell line is compared to that in normal endometrial epithelium using immunohistochemistry and flow cytometry and is confirmed by immunoprecipitation, Western immunoblot, and PCR. Like normal endometrial epithelium, Ishikawa cells maintain constitutive expression of alpha 2 beta 1, alpha 3 beta 1, alpha 6 beta 4. PCR demonstrates the expected size fragments of each, although evidence for alternatively spliced forms of the alpha 2-subunit was noted. Progesterone treatment of estradiol-primed cells resulted in increased expression of the alpha 1 beta 1 collagen-laminin receptor and suppression of the alpha v beta 3 vitronectin receptor, two of the cycle-dependent integrins expressed by normal endometrial epithelium. These data support the use of Ishikawa cells as an excellent model to study the regulation endometrial integrins and advance our understanding of hormonally mediated events surrounding implantation.