STAT3alpha is oncogenic for endometrial carcinoma cells and mediates the oncogenic effects of autocrine human growth hormone.

Abstract	We herein demonstrate an oncogenic role for signal transducer and activator of transcription (STAT)-3alpha (the full length STAT3 isoform), which also mediates autocrine human GH (hGH)-stimulated oncogenicity, in human endometrial carcinoma (EC) cells. Autocrine hGH stimulated Y705 phosphorylation of STAT3 and STAT3-mediated transcriptional activity in a SRC and Janus-2 Kinase dependent manner in human EC cell lines. Forced expression of a constitutively active variant of STAT3alpha increased proliferation, anchorage-independent, three-dimensional (3D) Matrigel, and xenograft growth and promoted epithelial-mesenchymal transition, migration, and invasion of EC cells. Conversely, the oncogenic capacity of EC cells was significantly impaired by treatment with JSI-124, an inhibitor of STAT3 phosphorylation and activity, small interfering RNA-mediated depletion of STAT3alpha, or a dominant-negative variant of STAT3alpha. Furthermore, the enhanced EC cell oncogenicity stimulated by autocrine hGH, was also abrogated by functional inhibition or small interfering RNA-mediated depletion of STAT3alpha. STAT3alpha may therefore be a common mediator of oncogenic signaling pathways stimulating progression of EC.
Authors	Jian-Zhong Tang, Xiang-Jun Kong, Arindam Banerjee, Nethaji Muniraj, Vijay Pandey, Michael Steiner, Jo K Perry, Tao Zhu, Dong-Xu Liu, Peter E Lobie
Journal	Endocrinology (Endocrinology) Vol. 151 Issue 9 Pg. 4133-45 (Sep 2010) ISSN: 1945-7170 [Electronic] United States
PMID	20668024 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Membrane Proteins STAT3 Transcription Factor Triterpenes delta-hGHR Human Growth Hormone cucurbitacin I
Topics	Animals Autocrine Communication (drug effects) Blotting, Western Cell Line, Tumor Cell Movement (drug effects) Cell Proliferation (drug effects) Endometrial Neoplasms (genetics, metabolism, pathology) Female Human Growth Hormone (genetics, metabolism, pharmacology) Humans Membrane Proteins (genetics, metabolism) Mice Mice, SCID Microscopy, Fluorescence Neoplasm Invasiveness Neoplasms, Experimental (genetics, metabolism, pathology) Phosphorylation RNA Interference STAT3 Transcription Factor (genetics, metabolism) Transplantation, Heterologous Triterpenes (pharmacology)

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