Fontana J A, Miranda D, Mezu A B
Department of Medicine, University of Maryland, Baltimore 21201.
Cancer Res. 1990 Apr 1;50(7):1977-82.
Retinoic acid (RA) inhibits proliferation of numerous breast carcinoma cells and prevents estrogen stimulation of growth of several estrogen receptor (ER)-positive cell lines. RA inhibition of human breast carcinoma cell proliferation is associated with marked inhibition of the synthesis of a Mr 39,000 protein in the ER-positive human breast carcinoma cell lines investigated. Inhibition of the synthesis of the Mr 39,000 protein occurred within 24 h of RA addition and coincides with the onset of inhibition of cellular proliferation. Increasing the dose of RA results in increasing inhibition of Mr 39,000 synthesis. RA does not inhibit the proliferation of the ER-negative human breast carcinoma cell line MDA MB-231; synthesis and inhibition of the Mr 39,000 protein is not noted in this cell line. Tamoxifen, which inhibits ER-positive breast carcinoma proliferation, moderately inhibits Mr 39,000 synthesis, while a concentration of difluoromethylornithine which inhibits cellular proliferation by greater than 50% does not affect Mr 39,000 protein synthesis. Thus, inhibition of the Mr 39,000 protein appears not to be simply related to the cessation of cellular proliferation.
视黄酸(RA)可抑制多种乳腺癌细胞的增殖,并阻止雌激素对几种雌激素受体(ER)阳性细胞系生长的刺激作用。在所研究的ER阳性人乳腺癌细胞系中,RA对人乳腺癌细胞增殖的抑制作用与一种分子量为39,000的蛋白质合成的显著抑制有关。添加RA后24小时内,分子量为39,000的蛋白质合成受到抑制,且与细胞增殖抑制的开始时间一致。增加RA的剂量会导致对分子量为39,000的蛋白质合成的抑制作用增强。RA不会抑制ER阴性人乳腺癌细胞系MDA MB - 231的增殖;在该细胞系中未观察到分子量为39,000的蛋白质的合成及抑制情况。抑制ER阳性乳腺癌细胞增殖的他莫昔芬会适度抑制分子量为39,000的蛋白质的合成,而浓度能使细胞增殖抑制超过50%的二氟甲基鸟氨酸并不影响分子量为39,000的蛋白质的合成。因此,对分子量为39,000的蛋白质的抑制似乎并非仅仅与细胞增殖的停止有关。