journal contribution
posted on 2023-03-30, 23:46 authored by David P. Labbé, Noriko Uetani, Valérie Vinette, Laurent Lessard, Isabelle Aubry, Eva Migon, Jacinthe Sirois, Jody J. Haigh, Louis R. Bégin, Lloyd C. Trotman, Marilène Paquet, Michel L. Tremblay Supplementary Materials and Methods, Supplementary Table, Supplementary References and Supplementary Figures S1 to S5
Funding
Canadian Institute of Health Research (CIHR)
Jeanne and Jean-Louis Lévesque Chair in Cancer Research
NIH
U.S. Army Department of Defense
CIHR
Prostate Cancer Canada
History
ARTICLE ABSTRACT
Diet affects the risk and progression of prostate cancer, but the interplay between diet and genetic alterations in this disease is not understood. Here we present genetic evidence in the mouse showing that prostate cancer 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 (encoding PTP1B) enables a highly invasive disease. Prostate cancer 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 prostate cancer, 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. Cancer Res; 76(11); 3130–5. ©2016 AACR.
