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细胞的抑制作用还可通过MAPK依赖性胰岛素反应

途径。Weng等¨列通过对乳腺癌模型的研究发现,

PTEN在胰岛素介导的信号转导途径中发挥独特作

用。在人乳腺癌细胞系7上皮性乳腺癌模型中,野

生型PTEN异位表达导致Akt磷酸化水平广泛抑制,

并且选择性抑制MAPK/ERK的磷酸化水平,而Akt

磷酸化水平受胰岛素和胰岛素生长因子1调控。

Bandyopadhyay等Ⅲ1在乳腺癌及前列腺癌中的研究

显示,PTEN上调肿瘤转移抑制基因Drg.1,而且

PTEN及Drg—l在临床标本中的表达呈显著正相关,

这也证明了PTEN可能通过上调Drg-l基因而发挥

其对乳腺癌转移的抑制作用。

5展望

PTEN基因通过P13K/Akt、MAPK/ERK、FAK等

途径发挥其脂质磷酸酶和蛋白磷酸酶活性。PTEN

基因及其蛋白表达异常与乳腺癌密切相关,野生型

PTEN基因能够对乳腺癌细胞产生抑制作用。但目

前对其详细的作用途径还没有完全明确,如对PTEN

的下游靶器的证明和PTEN在PDK-PTEN—Akt轴中

的基本角色认识仍不够完善,尚需深入研究。对

PTEN的转录规律、半衰期、细胞核区域化和PTEN

蛋白激活酶等的认知尚少。上述问题的解决将有助

于对PTEN的抑癌机制的阐明,更有助于肿瘤的早期

诊断和对肿瘤的基因治疗,对于研发新一代抗肿瘤

药物也具有重要的指导作用。

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收稿日期:2009-05-03修回日期:2009.1l-05

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