Retinoic acid nuclear receptor alpha(RAR alpha) plays a major role in retinoid-mediated inhibition of growth in human breast carcinoma cells.
Retinoids mediate their actions via retinoic acid receptors (RARs) and retinoid X receptors (RXRs). Each of class of these nuclear retinoid receptor is further subdivided into three species namely alpha, beta and gamma. Recently studies demonstrated that estrogen receptor (ER)-positive human breast cancer (HBC) cell lines are sensitive and ER-negative cell lines are resistant to growth inhibitory effects of retinoic acid (RA). In this study, we found that only RAR alpha mRNA levels was strongly correlated with ER-status. To further investigate the major role of RAR alpha in retinoid-mediated inhibition of growth, we transfected RAR alpha cDNA into two RA-resistant ER-negative HBC cell lines. Analysis of different clonal populations of RAR alpha transfectants from each cell line revealed growth inhibition by retinoids. Our results demonstrated that RAR alpha plays a major role in mediating retinoids inhibition of growth in HBC cells and adequate levels of RAR alpha are required for such an effect.
Shao
Z
Z
Department of Surgery, Cancer Hospital, Shanghai Medical University.
Yu
L
L
Shen
Z
Z
Fontana
J A
JA
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D012333:RNA, Messenger / Q000096:biosynthesis; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014212:Tretinoin