Abstract:
PURPOSE:Endometrial adenocarcinoma, due to a frequent activation of PI3 K/AKT has been proposed as a candidate neoplasm for the treatment with mTOR inhibitors. Yet, data on the expression of mTOR cascade components in endometrial cancer are lacking. METHODS:To provide a basis for futher studies with mTOR inhibitors, we used immunohistochemistry to evaluate the expression of activated mTOR pathway components in 57 endometrial cancer surgical specimens in vivo, and investigated in vitro the relation between the activation of AKT/mTOR and the response to rapamycin. RESULTS:p-mTOR expression was associated with nuclear p-4EBP1 expression (P = 0.02), and was more frequent in tumors extending ouside the uterine corpus (P = 0.011). Nuclear p-4EBP1 expression was increased in carcinomas of poor differentiation (P = 0.012). In cultivated PTEN-deficient Ishikawa cells, in addition to an activation of AKT, a phosphorylation of mTOR and 4EBP1 was evident, while PTEN-wild type HEC-1A cells lacked AKT activation but revealed a reduced expression of p-mTOR and p-4EBP1. Rapamycin induced a growth reduction, which was clearly more pronounced in Ishikawa cells than in HEC-1A cells (P < 0.03) and could be observed for up to 6 days. CONCLUSISONS: Expression of mTOR and 4EBP1 characterize high-grade, high-stage endometrial adenocarcinomas and might be predictive markers of a response to rapamycin. Based on our results, we suggest that the expression of elements of the mTOR pathway in human tumor tissue should be further evaluated as a possible predictive marker in large-scale clinical studies as well as translational research protocols in clinical studies with mTOR inhibitors.
journal_name
J Cancer Res Clin Oncoljournal_title
Journal of cancer research and clinical oncologyauthors
Darb-Esfahani S,Faggad A,Noske A,Weichert W,Buckendahl AC,Müller B,Budczies J,Röske A,Dietel M,Denkert Cdoi
10.1007/s00432-008-0529-5subject
Has Abstractpub_date
2009-07-01 00:00:00pages
933-41issue
7eissn
0171-5216issn
1432-1335journal_volume
135pub_type
杂志文章abstract::A previous cohort-study in a cardboard factory demonstrated that high and prolonged occupational exposure to trichloroethene (C2HCl3) is associated with an increased incidence of renal cell cancer. The present hospital-based case/control study investigates occupational exposure in 58 patients with renal cell cancer wi...
journal_title:Journal of cancer research and clinical oncology
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journal_title:Journal of cancer research and clinical oncology
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journal_title:Journal of cancer research and clinical oncology
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journal_title:Journal of cancer research and clinical oncology
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journal_title:Journal of cancer research and clinical oncology
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journal_title:Journal of cancer research and clinical oncology
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journal_title:Journal of cancer research and clinical oncology
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journal_title:Journal of cancer research and clinical oncology
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