[Expression and activation of insulin receptor substrate-1 in endometrial carcinoma].
OBJECTIVE
To investigate the mRNA, protein expression and tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) in endometrial carcinoma.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Hua
Shao-fang
SF
Department of Obstetrics and Gynecology, General Hospital, Tianjin Medical University, Tianjin 300052, China.
Xue
Feng-xia
FX
Zhang
Li-zhi
LZ
Wang
Ying-mei
YM
Zhao
Jing
J
D000230:Adenocarcinoma / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D002096:C-Peptide / Q000097:blood; D016022:Case-Control Studies; D004714:Endometrial Hyperplasia / Q000097:blood / Q000378:metabolism / Q000473:pathology; D016889:Endometrial Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014443:Tyrosine / Q000378:metabolism*
D002096:C-Peptide; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D012333:RNA, Messenger; D014443:Tyrosine