Autocrine human growth hormone stimulates oncogenicity of endometrial carcinoma cells.
Recent published data have demonstrated elevated levels of human GH (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 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 tumor 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 functional role for autocrine hGH in the development and progression of endometrial carcinoma and indicate potential therapeutic relevance of hGH antagonism in the treatment of endometrial carcinoma.
Pandey
Vijay
V
Liggins Institute and National Research Centre for Growth and Development, University of Auckland, 2-6 Park Avenue, Private Bag 92019 Auckland, New Zealand.
Perry
Jo K
JK
Mohankumar
Kumarasamypet M
KM
Kong
Xiang-Jun
XJ
Liu
Shu-Min
SM
Wu
Zheng-Sheng
ZS
Mitchell
Murray D
MD
Zhu
Tao
T
Lobie
Peter E
PE
D000818:Animals; D019898:Autocrine Communication / Q000502:physiology*; D002277:Carcinoma / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016889:Endometrial Neoplasms / Q000473:pathology*; D005260:Female; D019382:Human Growth Hormone / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D047368:Tumor Burden / Q000187:drug effects; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
C422172:B 2036; D019382:Human Growth Hormone