Hua Shao-fang, Xue Feng-xia, Zhang Li-zhi, Wang Ying-mei, Zhao Jing
Department of Obstetrics and Gynecology, General Hospital, Tianjin Medical University, Tianjin 300052, China.
Zhonghua Fu Chan Ke Za Zhi. 2008 Jun;43(6):437-41.
To investigate the mRNA, protein expression and tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) in endometrial carcinoma.
Sixty-three endometrial carcinoma (EC) patients, 21 endometrial atypical hyperplasia (AHE) patients and 22 normal control (NE) entered this study. Their clinical information were collected. Fasting serum C-peptide concentration was measured. Expression of IRS-1 in endometrium was examined by RT-PCR and western blot. Immunoprecipitation was used to measure the tyrosine phosphorylation of IRS-1.
C-peptide concentration in EC group was higher than that in NE group [(3.2 +/- 1.1) vs (2.5 +/- 0.7) microg/L, P=0.007]. There were no significant differences in IRS-1 mRNA and protein expression among the three groups. Tyrosine phosphorylation of IRS-1 in EC group [(62 +/- 36) %] was higher than that in AHE and NE groups [(53 +/-34)% and (35 +/- 33)%; P=0.048, 0.002]. IRS-1 activation in AHE group was also higher than normal control (P=0.045). IRS-1 activation in endometrioid carcinoma [(69 +/- 33) %] was higher than that in other histological types [(34 +/- 31)%; t=2.300, P=0.025]. IRS-1 tyrosine phosphorylation was significantly higher in patients with advanced stage, high grade, deep myometrial invasion and pelvic lymph node metastasis. IRS-1 activation in endometrium was positively correlated with fasting serum C-peptide concentration (r=0.491, P=0.001).
There is excessive activation of IRS-1 in endometrial carcinoma and atypical hyperplasia. Activation of IRS-1 in endometrial carcinoma is related with poor clinical-pathologic features and may be a prognostic predictor for this tumor. Over-activation of IRS-1 may be an intermediate event linking the hyperinsulinemia and endometrial carcinoma.
研究胰岛素受体底物-1（IRS-1）在子宫内膜癌中的mRNA、蛋白表达及酪氨酸磷酸化情况。
63例子宫内膜癌（EC）患者、21例子宫内膜非典型增生（AHE）患者及22例正常对照者（NE）纳入本研究。收集其临床资料，测定空腹血清C肽浓度。采用逆转录-聚合酶链反应（RT-PCR）和蛋白质印迹法检测子宫内膜中IRS-1的表达。用免疫沉淀法检测IRS-1的酪氨酸磷酸化水平。
EC组C肽浓度高于NE组[（3.2±1.1）对（2.5±0.7）μg/L，P=0.007]。三组间IRS-1 mRNA和蛋白表达无显著差异。EC组IRS-1的酪氨酸磷酸化水平[（62±36）%]高于AHE组和NE组[（53±34）%和（35±33）%；P=0.048，0.002]。AHE组IRS-1的激活水平也高于正常对照组（P=0.045）。子宫内膜样癌中IRS-1的激活水平[（69±33）%]高于其他组织学类型[（34±31）%；t=2.300，P=0.025]。晚期、高级别、肌层浸润深及盆腔淋巴结转移患者的IRS-1酪氨酸磷酸化水平显著更高。子宫内膜中IRS-1的激活与空腹血清C肽浓度呈正相关（r=0.491，P=0.001）。
子宫内膜癌和非典型增生中存在IRS-1的过度激活。子宫内膜癌中IRS-1的激活与不良临床病理特征相关，可能是该肿瘤的预后预测指标。IRS-1的过度激活可能是连接高胰岛素血症和子宫内膜癌的中间事件。
