Tumorigenesis of K-ras mutation in human endometrial carcinoma via upregulation of estrogen receptor

Tu, Zheng, Gui, Liming, Wang, Jianliu, Li, Xiaoping, Sun, Pengming and Wei, Lihui 2006. Tumorigenesis of K-ras mutation in human endometrial carcinoma via upregulation of estrogen receptor. Gynecologic Oncology 101 (2) , pp. 274-279. 10.1016/j.ygyno.2005.10.016

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Abstract

Objective. To investigate the tumorigenesis of mutant [12Asp]-K-ras in endometrial carcinoma and its relationship with ER. Methods. We constructed pcDI-[12Asp]K-ras4B by inserting full-length [12Asp]K-ras4B from human endometrial carcinoma Hec-1A cells, into pcDI vector. Cell proliferation of NIH3T3 after transfection with pcDI-[12Asp]K-ras4B was measured by MTT assay. The cell transformation was determined by colony formation and tumor nodule development. [12Asp]-K-ras4B-NIH3T3 cells were transfected with constitutively active pCMV-RafCAAX and dominant-negative pCMV-RafS621A. Cell growth was measured by MTT assay and [3H]thymidine incorporation. After transfected with pcDI-[12Asp]K-ras4B or pCMV-RafS621A, the cells were harvested for Western blot and reporter assay to determine the expression and transcriptional activity of ERα and ERβ, respectively. Results. [12Asp]-K-ras4B enhanced NIH3T3 cells proliferation after 48 h post-transfection (P < 0.05). More colonies were grown 10 days after incubating pcDI-[12Asp]-K-ras4B-NIH3T3 cells (13.48%) than pcDI-NIH3T3 (4.26%) or untreated NIH3T3 (2.33%). The pcDI-[12Asp]-K-ras4B-NIH3T3 cells injected to the nude mice Balb/C developed tumor nodules with poor-differentiated cells after 12 days. An increase of ERα and ERβ was observed in pcDI-[12Asp]-K-ras4B-NIH3T3 cells. RafS621A downregulated ERα and ERβ expression. Estrogen induced the ER transcriptional activity by 5-fold in pcDI-NIH3T3 cells, 13-fold in pcDI-[12Asp]K-ras4B-NIH3T3 and 19-fold in HEC-1A. RafS621A suppressed the ER transcriptional activity. Conclusions. K-ras mutation induces tumorigenesis in endometrium, and this malignant transformation involves Raf signaling pathway and ER.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences European Cancer Stem Cell Research Institute (ECSCRI)
Publisher:	Elsevier
ISSN:	0090-8258
Last Modified:	28 Jun 2019 02:02
URI:	https://orca.cardiff.ac.uk/id/eprint/63363

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