Expression and activation of insulin receptor substrate-1 in endometrial carcinoma

Abstract

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.