Shao Z M, Alpaugh M L, Fontana J A, Barsky S H
Department of Pathology and Revlon/UCLA Breast Center, UCLA School of Medicine 90024, USA.
J Cell Biochem. 1998 Apr 1;69(1):44-54.
Genistein has been proposed to be responsible for lowering the rate of breast cancer in Asian women but the mechanism for this chemopreventive effect in vivo is unknown. In this study, we present in vitro evidence that genistein inhibits cell proliferation similarly in ER-positive and ER-negative human breast carcinoma cell lines. This inhibition is associated with specific G2/M arrest and induction of p21WAF1/CIP1 expression. Genistein results in a five-to six-fold increase in p21WAF1/CIP1 mRNA levels and a three- to four-fold increase in protein levels, only a 1.5-fold increase in p21WAF1/CIP1 transcription but a three- to six-fold increase in p21WAF1/CIP1 mRNA stability. The increase in p21WAF1/CIP1 is followed by increased apoptosis. The similar effects of genistein on a number of breast carcinoma cell lines with different ER and p53 status suggest that the actions of genistein reported here are mediated through ER and p53 independent mechanisms. The chemopreventive effects of genistein in vivo could be mediated along an identical or similar anti-proliferative pathway.
染料木黄酮被认为是亚洲女性乳腺癌发病率较低的原因，但这种体内化学预防作用的机制尚不清楚。在本研究中，我们提供了体外证据，表明染料木黄酮在雌激素受体（ER）阳性和ER阴性的人乳腺癌细胞系中对细胞增殖的抑制作用相似。这种抑制与特定的G2/M期阻滞和p21WAF1/CIP1表达的诱导有关。染料木黄酮使p21WAF1/CIP1 mRNA水平增加五到六倍，蛋白质水平增加三到四倍，p21WAF1/CIP1转录仅增加1.5倍，但p21WAF1/CIP1 mRNA稳定性增加三到六倍。p21WAF1/CIP1增加后细胞凋亡增加。染料木黄酮对许多具有不同ER和p53状态的乳腺癌细胞系具有相似作用，表明此处报道的染料木黄酮作用是通过不依赖ER和p53的机制介导的。染料木黄酮在体内的化学预防作用可能是通过相同或相似的抗增殖途径介导的。
