Anticancer Research, 2010, 30(6):2049-54.

AKT and p21^WAF1/CIP1 as potential genistein targets in BRCA1-mutant human breast cancer cell lines

MAUD PRIVAT, MARC FERRARA, et al

Centre Jean Perrin, Département d'Oncogénétique, F-63000 Clermont-Ferrand, France; et al

BRCA1 acts as a tumour suppressor and germ-line mutations within this gene are found in a large proportion of families with breast cancer. The aim of our study was to unravel the mechanism of action of genistein, the major soy phytoestrogen, in BRCA1-mutant human breast cancer cell lines. Four breast cancer cell lines were studied for their response to genistein, three of them harbouring different mutations within the BRCA1 gene (HCC1937, SUM149 and SUM1315 cells) and the MDA-MB-231 cell line, which expresses a functional BRCA1 protein. We showed that genistein inhibits proliferation and induces apoptosis more efficiently in BRCA1-mutant cells than in cells expressing wild-type BRCA1 protein. Increased AKT and decreased p21(WAF1/CIP1) protein levels could explain the relative resistance to genistein elicited by cells with wild-type BRCA1. BRCA1-mutant breast cancer cells are highly sensitive to genistein treatment and p21(WAF1/CIP1) and AKT could be genistein targets in these cells.

希腊《抗癌研究》，2010年6月

在 BRCA1- 突变人类乳腺癌细胞系中AKT 和 p21^WAF1/CIP1可以作为潜在的金雀异黄素靶标

莫 普里瓦，马克 费拉拉等

法国遗传学让 · 佩林中心等

Brca1 基因作为一个肿瘤抑制和种系突变基因被发现在乳腺癌患者中占有很大比重。我们研究的目的是阐述染料木黄酮这种主要的大豆植物雌激素在 BRCA1 突变人类乳腺癌细胞中的活动机制。研究四个乳腺癌细胞对染料木素的响应，其中三个包含了BRCA1 基因的不同的突变（HCC1937、 SUM149 和 SUM1315 细胞） ，而在MDA –MB- 231 细胞中功能性BRCA1 蛋白得到了表达。我们发现，染料木黄酮在 BRCA1 突变细胞中比野生型表达BRCA1 蛋白细胞能更有效地抑制增殖并诱导细胞凋亡。提高AKT 并降低 p21^WAF1/CIP1 蛋白的水平可以解释野生型 BRCA1细胞诱发的对染料木黄酮的抗性。Brca1- 基因突变乳腺癌细胞对染料木黄酮治疗高度敏感，并且在这些细胞中p21^WAF1/CIP1 和 AKT 可能是金雀异黄素的靶标。