NDLI: Hepatocyte growth factor-like protein is required for prostate tumor growth in the TRAMP mouse model

Content Provider	PubMed Central
Author	Vasiliauskas, Juozas Nashu, Madison A. Pathrose, Peterson Starnes, Sandra L. Waltz, Susan E.
Copyright Year	2014
Abstract	The Ron receptor is deregulated in a variety of cancers. Hepatocyte growth factor-like protein (HGFL) is the ligand for Ron and is constitutively secreted from hepatocytes into the circulation. While a few recent reports have emerged analyzing ectopic HGFL overexpression in cancer cells, no studies have examined the effect of host-produced HGFL in tumorigenesis. To examine HGFL function in prostate cancer, the TRAMP mouse model, which is predisposed to develop prostate tumors, was utilized. Prostate tumors from TRAMP mice exhibit elevated levels of HGFL, which correlated with upregulation in human prostate cancer. To directly implicate HGFL in prostate tumorigenesis, TRAMP mice deficient in HGFL (HGFL-/-TRAMP+) were generated. HGFL-/- TRAMP+ mice developed significantly smaller prostate tumors compared to controls. Analysis of HGFL-/- tumors revealed reduced tumor vascularization. No differences in cancer cell proliferation were detected between HGFL-/- TRAMP+ and HGFL+/+ TRAMP+ mice. However, a significant increase in cancer cell death was detected in HGFL-/- TRAMP+ prostates which correlated with decreased pro-survival targets. In vitro analysis demonstrated robust STAT3 activation resulting in Bcl2-dependent survival following treatment of prostate cancer cells with HGFL. These data document a novel function for endogenous HGFL in prostate cancer by imparting a critical survival signal to tumor cells.
Related Links	http://dx.doi.org/10.18632/oncotarget.2139
Ending Page	5558
Page Count	12
Starting Page	5547
File Format	PDF
ISSN	19492553
e-ISSN	19492553
Journal	Oncotarget
Issue Number	14
Volume Number	5
Language	English
Publisher	Impact Journals LLC
Publisher Date	2014-08-01
Access Restriction	Open
Rights Holder	Impact Journals LLC
Subject Keyword	Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Oncology

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