HOXA10 regulates p53 expression and matrigel invasion in human breast cancer cells
HOXA10 regulates p53 expression and matrigel invasion in human breast cancer cells
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DOI：
10.4161/cbt.3.6.848
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发表时间：
2004-06-01
影响因子：
3.6
通讯作者：
Taylor, HS
中科院分区：
文献类型：
--
作者：
Chu, MC;Selam, FB;Taylor, HS
HOX 基因调节胚胎发育过程中的细胞分化。在这里，我们证明了 HOXA10 在良性和恶性成人乳腺组织以及 MCF-7 中表达，但在 BT20 乳腺癌细胞中不表达。我们之前已经证明 HOXA10 介导子宫分化以响应雌激素。雌二醇和其他雌激素受体调节剂对乳腺癌细胞生长的作用机制仍知之甚少。 ER (+) 并表达 HOXA10 的 MCF-7 细胞用于测定雌二醇和他莫昔芬对 HOXA10 表达的影响。半定量 RT-PCR 和 Northern 分析表明，雌二醇或他莫昔芬治疗可增加 HOXA10 mRNA 表达。 BT20 细胞为 ER (-) 并且不内源表达 HOXA10，用于测定 HOXA10 表达增加对 p53 表达和侵袭表型的影响。在 BT20 细胞中组成型表达 HOXA10 会增加 p53 蛋白的表达。 HOXA10 的增加也减少了基质胶的侵袭性。雌激素和其他雌激素受体调节剂影响正常乳房发育和乳腺癌的机制可能涉及发育控制基因（例如 HOXA10）的调节； HOXA10 反过来调节 p53 等关键下游基因的表达并调节肿瘤细胞功能表型。
HOX genes regulate cell differentiation during embryonic development. Here we demonstrate HOXA10 expression in both benign and malignant adult human breast tissue and in MCF-7, but not BT20 breast cancer cells. We have previously shown that HOXA10 mediates uterine differentiation in response to estrogens. The mechanism of action of estradiol and other estrogen receptor modulators on breast cancer cell growth is still poorly understood. MCF-7 cells, which are ER (+) and express HOXA10, were used to assay the effect of estradiol and tamoxifen on HOXA10 expression. Semi-quantitative RT-PCR and northern analysis revealed that treatment with either estradiol or tamoxifen increased HOXA10 mRNA expression. BT20 cells, which are ER (-) and do not endogenously express HOXA10, were used to assay the effect of increased HOXA10 expression on p53 expression and on the invasive phenotype. Constitutively expressing HOXA10 in BT20 cells increased p53 protein expression. Increased HOXA10 also reduced invasiveness through matrigel. The mechanism by which estrogen and other estrogen receptor modulators influence both normal breast development as well as breast cancer may involve the regulation of developmental control genes such as HOXA10; HOXA10 in turn regulates expression of key downstream genes such as p53 and regulates tumor cell functional phenotype.