Sensitivity of Primary Breast Cancer Cells to Retinoids Protein Clinical Implications

摘要

Our main goal in this study is to evaluate the sensitivity of primary breast cancer cells (PBCCs) grown both in vitro and in vivo (nude mice) to retinoids. Contrary to most previous studies on established breast cancer cell lines, in this study we assessed the effects of retinoids all-trans retinoic acid (atRA), 9-cis retinoic acid (9cisRA) and 4-(hydroxyphenyl)retinamide (4- HPR) on PBCCs grown both, in vitro (first several passages) and in nude mice. Tissue samples from 16 breast carcinomas were cultured in vitro and in 10 of them (62.5%) satisfactory growth was found. We optimized the protocol for assessment ER, retinoic acid receptors (RAR-alpha, beta, 7), and retinoid X receptors (RAR-alpha, beta, gamma) in paraffin sections from breast tumors as well as in cells growing in vitro. We found that 7 from 16 tumors were ER negative, that RARalpha was expressed in 14, RARbeta in 10, RARgamma in 15, from 16 tumors respectively. In 60% of tumors RARbeta was expressed both in nucleus and cytoplasm. RXRalphaa and RXRgamma were also expressed both in 15 from 16 tumors. Cells from 5 tumors were implanted in nude mice and 4 indicated satisfactory growth. Tumor cells cultured in vitro, as well as growing in nude mice are currently under investigation for assessment the effects of various retinoids on cell proliferation and cell death-related markers.