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首页> 外文期刊>Cancer Cell >Histologically normal human mammary epithelia with silenced p16(INK4a) overexpress COX-2, promoting a premalignant program.
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Histologically normal human mammary epithelia with silenced p16(INK4a) overexpress COX-2, promoting a premalignant program.

机译:p16(INK4a)沉默的组织学正常的人类乳腺上皮细胞过表达COX-2,促进了癌前程序。

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摘要

Breast tissue from healthy women contains variant mammary epithelial cells (vHMEC) exhibiting p16(INK4a) promoter hypermethylation both in vivo and in vitro. When continuously cultured, vHMEC acquire telomeric dysfunction and produce the types of chromosomal abnormalities seen in premalignant lesions of cancer. We find that late passage vHMEC express elevated prostaglandin cyclo-oxygenase 2 (COX-2), which contributes to increased prostaglandin synthesis, angiogenic activity, and invasive ability. These data demonstrate the existence of human mammary epithelial cells with the potential to acquire multiple genomic alterations and phenotypes associated with malignant cells. Moreover, COX-2 overexpression coincides with focal areas of p16(INK4a) hypermethylation in vivo, creating ideal candidates as precursors to breast cancer. These putative precursors can be selectively eliminated upon exposure to COX-2 inhibitors in vitro.
机译:健康女性的乳房组织包含变异的乳腺上皮细胞(vHMEC),在体内和体外均表现出p16(INK4a)启动子高度甲基化。连续培养后,vHMEC会出现端粒功能障碍,并产生在癌变前病变中见到的染色体异常类型。我们发现,晚期传代vHMEC表达升高的前列腺素环加氧酶2(COX-2),这有助于增加前列腺素的合成,血管生成活性和侵袭能力。这些数据证明了人类乳腺上皮细胞的存在,其具有获得与恶性细胞相关的多种基因组改变和表型的潜力。此外,COX-2的过表达与体内p16(INK4a)甲基化过度的局灶区域相吻合,从而创造了理想的候选乳腺癌候选物。在体外暴露于COX-2抑制剂后,可以有选择地消除这些假定的前体。

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