TY - JOUR T1 - Loss of Anti-proliferative Effect of All-<em>trans</em> Retinoic Acid in Advanced Stage of Breast Carcinogenesis JF - Anticancer Research JO - Anticancer Res SP - 2899 LP - 2904 VL - 29 IS - 8 AU - EUN HYUN AHN AU - CHIA-CHENG CHANG AU - DAVID A. TALMAGE Y1 - 2009/08/01 UR - http://ar.iiarjournals.org/content/29/8/2899.abstract N2 - Background: Mechanisms by which the inhibitory effect of retinoic acid on tumor growth is attenuated as tumors progress to more advanced stages are unclear. Materials and Methods: This study utilizes a novel cell culture system of human breast epithelial cells (HBEC). Immortal (M13SV1), weakly tumorigenic (M13SV1-R2), and highly tumorigenic (M13SV1-R2N1) transformed Type I HBEC were derived sequentially from the same parental Type I HBEC (stem cells) developed from reduction mammoplasty of healthy women. Effects of all-trans retinoic acid (AT-RA) on the growth, protein expression of RAR-α, β and γ, and RARE transcriptional activation were determined. Results and Conclusion: AT-RA reduces proliferation rates of immortal and weakly tumorigenic cells, but not highly tumorigenic cells. This loss of response of highly tumorigenic cells to AT-RA is associated with overexpression of p185c-erbB2/neu. It is not associated with decreased RAR-α, β or γ expression, or activation by AT-RA; RAR-α, β and γ are expressed and AT-RA increases RARE transcriptional activity in all cell lines tested in this study. ER -