Soprano D R, Chen L X, Wu S, Donigan A M, Borghaei R C, Soprano K J
Department of Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Oncogene. 1996 Feb 1;12(3):577-84.
Retinoids including retinoic acid (RA) have been demonstrated to be effective growth inhibitors of a number of human cancer cell lines including ovarian adenocarcinoma cells. To begin to determine the mechanism of action by which RA inhibits the growth of ovarian carcinoma cells, we have examined AP-1 activity in two representative cell lines: CaOV-3 a RA-sensitive cell line and SK-OV-3 a RA-resistant cell line. AP-1 activity was found to be inhibited by 50% upon RA treatment of the RA-sensitive cells while there was no change in AP-1 activity following RA treatment of the RA-resistant cells. Maximal inhibition of AP-1 activity could be achieved in the RA-resistant SK-OV-3 cells by overexpression of any one of the three retinoic acid receptor (RAR) subtypes in conjunction with retinoid X receptor (RXR) alpha. This inhibition of AP-1 activity was nearly comparable to that of the RA-sensitive cells. A similar change in AP-1 complex formation in vitro has also been observed. These results suggest that one mechanism by which RA inhibits growth of RA-sensitive ovarian carcinoma cells is by repressing AP-1 activity. Moreover, in the RA-resistant cells the RAR/RXR signalling pathway leading to inhibition of AP-1 activity is impaired however overexpression of one of the RAR subtypes along with RXR alpha is sufficient to restore this pathway.
包括视黄酸（RA）在内的类视黄醇已被证明是多种人类癌细胞系（包括卵巢腺癌细胞）的有效生长抑制剂。为了开始确定RA抑制卵巢癌细胞生长的作用机制，我们检测了两种代表性细胞系中的AP-1活性：对RA敏感的CaOV-3细胞系和对RA耐药的SK-OV-3细胞系。在对RA敏感的细胞中，RA处理后AP-1活性被发现受到50%的抑制，而在对RA耐药的细胞中，RA处理后AP-1活性没有变化。通过过表达三种视黄酸受体（RAR）亚型中的任何一种与视黄醇X受体（RXR）α结合，可在对RA耐药的SK-OV-3细胞中实现AP-1活性的最大抑制。这种对AP-1活性的抑制与对RA敏感的细胞几乎相当。在体外也观察到AP-1复合物形成的类似变化。这些结果表明，RA抑制对RA敏感的卵巢癌细胞生长的一种机制是通过抑制AP-1活性。此外，在对RA耐药的细胞中，导致AP-1活性抑制的RAR/RXR信号通路受损，然而，一种RAR亚型与RXRα的过表达足以恢复该通路。
