Vitamin A Regulation of Cadherins in Breast Cancer.

摘要

Vitamin a derivatives (retinoids) are known to be potent regulators of cell proliferation and epithelial cell differentiation and specifically inhibit the growth of several cancers. The mechanisms of action of retinoids are just starting to be understood. For example, retinoids are known to inhibit the junction of AP-1, a transcription factor complex that is involved in cell proliferation and neoplastic transformation. Retinoids are also known to stabilize components of the adherens junction, the junction of which is essential in preventing tumor progression and invasion. Previously, we have shown that in a breast cancer cell line, 9-cis retinoic acid induces a dramatic change in cell morphology, an increase in cell-cell adhesion strength, a decrease in cell proliferation, and an increase in the expression of the adherens junction molecule, beta-catenin. This work now demonstrates that retinoic acid also induces the expression of a cadherin and that the expression of a cadherin, not of beta-catenin is necessary and sufficient to mimic the effects induced by retinoic acid. Furthermore, this work also gives strong evidence to suggest that retinoic acid inhibits the beta-catenin mediated cell signaling pathway, although in a manner independent of cadherin function.