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This version published online on May 1, 2008
Endocrinology, doi:10.1210/en.2008-0286
A more recent version of this article appeared on August 1, 2008
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*Substance via MeSH

Submitted on February 29, 2008
Accepted on April 14, 2008

Autocrine Human Growth Hormone Stimulates Oncogenicity of Endometrial Carcinoma Cells

Vijay Pandey, Jo K Perry, Kumarasamypet M. Mohankumar, Xiang-Jun Kong, Shu-Min Liu, Zheng-Sheng Wu, Murray D. Mitchell, Tao Zhu*, and Peter E. Lobie*

Liggins Institute and National Research Centre for Growth and Development, and Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand; Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, P.R. China; Department of Pathology, Anhui Medical University, Hefei, Anhui 230032, P.R. China

* To whom correspondence should be addressed. E-mail: zhut{at}ustc.edu.cn or p.lobie{at}auckland.ac.nz.

Recent published data has demonstrated elevated levels of hGH in endometriosis and endometrial adenocarcinoma. Herein, we demonstrate that autocrine production of hGH can enhance the in vitro and in vivo oncogenic potential of endometrial carcinoma cells. Forced expression of hGH in the endometrial carcinoma cell lines, RL95-2 and AN3, resulted in an increased total cell number through enhanced cell cycle progression and decreased apoptotic cell death. In addition, autocrine hGH expression in endometrial carcinoma cells promoted anchorage-independent growth and increased cell migration/invasion in vitro. In a xenograft model of human endometrial carcinoma, autocrine hGH enhanced tumour size and progression. Changes in endometrial carcinoma cell gene expression stimulated by autocrine hGH was consistent with the altered in vitro and in vivo behavior. Functional antagonism of hGH in wild-type RL95-2 cells significantly reduced cell proliferation, cell survival and anchorage-independent cell growth. These studies demonstrate a pivotal role for autocrine hGH in the development and progression of endometrial carcinoma and indicates potential therapeutic relevance of hGH antagonism in the treatment of endometrial carcinoma.
Key words: growth hormone • endometrial carcinoma • oncogenesis






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