PTP1B deficiency enables the ability of a high fat diet to drive the invasive character of PTEN-deficient prostate cancers

Labbe, D. P., Uetani, N., Vinette, V., Lessard, L., Aubry, I., Migon, E., Sirois, J., Haigh, J., Begin, L. R., Trotman, L. C., Paquet, M., Tremblay, M. L. (June 2016) PTP1B deficiency enables the ability of a high fat diet to drive the invasive character of PTEN-deficient prostate cancers. Cancer Res, 76 (11). pp. 3130-3135. ISSN 1538-7445 (Electronic)0008-5472 (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/27020859
DOI: 10.1158/0008-5472.can-15-1501

Abstract

Diet affects the risk and progression of prostate cancer (PCa), but the interplay between diet and genetic alterations in this disease is not understood. Here we present genetic evidence in the mouse showing that PCa progression driven by loss of the tumor suppressor Pten is mainly unresponsive to a high fat diet (HFD), but that coordinate loss of the protein tyrosine phosphatase Ptpn1 (PTP1B in human) enables a highly invasive disease. PCa in Pten-/-Ptpn1-/- mice was characterized by increased cell proliferation and Akt activation, interpreted to reflect a heightened sensitivity to IGF-1 stimulation upon HFD feeding. Prostate-specific overexpression of PTP1B was not sufficient to initiate PCa, arguing that it acted as a diet-dependent modifier of prostate cancer development in Pten-/- mice. Our findings offer a preclinical rationale to investigate the anticancer effects of PTP1B inhibitors currently being studied clinically for diabetes treatment as a new modality for management of prostate cancer.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > PTEN
diseases & disorders > cancer > cancer types > prostate cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > protein tyrosine phosphatase
CSHL Authors:
Communities: CSHL labs > Trotman lab
CSHL Cancer Center Program > Signal Transduction
Depositing User: Matt Covey
Date: 1 June 2016
Date Deposited: 01 Apr 2016 20:31
Last Modified: 05 Mar 2018 15:45
PMCID: PMC4891239
Related URLs:
URI: http://repository.cshl.edu/id/eprint/32477

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