CDK2-AP1通过调控细胞周期抑制乳腺癌生长

目的探讨CDK2-AP1在乳腺癌的作用及其机制。方法分别在正常乳腺组织及不同分期乳腺癌组织中检测CDK2-AP1的表达情况；进行CDK2-AP1的LOF＆GOF细胞功能实验；接种CDK2-APl干扰或过表达的乳腺癌细胞及对照细胞在裸鼠观察成瘤及相应指标。结果在乳腺癌存在CDK2-AP1表达降低／缺失CDK2／CyclinDl表达升高的情况，且CDK2-AP1的表达在正常乳腺组织细胞、乳腺导管原位癌、侵袭性乳腺癌、复发转移性乳腺癌渐次降低（P〈O．001），与CDK2／CyclinDl相反。体内、外实验均发现抑制CDK2-AP1表达后乳腺癌细胞周期后移、增殖加快；过表达CDK2-AP1的乳腺癌细胞周期阻滞在G0／G和G2／M期，生长受抑制、裸鼠成瘤速度及大小均受抑制。结论CDK2-AP1的表达降低以至缺失促进乳腺细胞进入恶性增殖形成肿瘤，缺乏细胞周期负性调控的乳腺癌细胞增殖能力增强。

Objective To observe the role of CDK2-AP1 in breast cancer. Methods Expressions of CDK2-AP1, CDK2 and CyclinD1 were examined in 209 cases of pathological specimens using IHC staining. Lost-of-fimetion and Gain-of-function assays were performed in vivo and in vitro to assess the specific role of CDK2-AP1 in breast cancer. Results The positive ratio of CDK2-AP1 expression was reduced successively in normal breast tissue, DCIS, invasive breast cancer and relapsed breast cancer, suggesting that CDK2-AP1 was correlated closely with the tumor＇ s genesis and progress and might work as a tumor suppressor. After down-regulating CDIC2-APt in breast cancer cells, the cell cycle was accelerated and the cell proliferation was promoted. The cell cycle was arrested in G0/G1 phase and G2/M phase after up-regulating CDK2-AP1 in breast cancer cells, resulting. in inhibited cell proliferation. The same results were obtained by animal assays. Conclusions CDK2-AP1 affects tumor genesis and tumor growth by cell cycle regulation, which has the potential to be a therapeutic agent in breast cancer.