title: PTP1B Deficiency Enables the Ability of a High-Fat Diet to Drive the Invasive Character of PTEN-Deficient Prostate Cancers.
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.
authors.affiliation: Goodman Cancer Research Centre, McGill University, Montréal, Québec, Canada. Division of Experimental Medicine, Department of Medicine, McGill University, Montréal, Québec, Canada.
authors.forename: David P
authors.initials: DP
authors.lastname: Labbé
authors.affiliation: Goodman Cancer Research Centre, McGill University, Montréal, Québec, Canada.
authors.forename: Noriko
authors.initials: N
authors.lastname: Uetani
authors.affiliation: Goodman Cancer Research Centre, McGill University, Montréal, Québec, Canada. Department of Biochemistry, McGill University, Montréal, Québec, Canada.
authors.forename: Valérie
authors.initials: V
authors.lastname: Vinette
authors.affiliation: Research Group in Molecular Oncology and Endocrinology, Department of Medical Biology, Université du Québec à Trois-Rivières, Trois-Rivières, Québec, Canada.
authors.forename: Laurent
authors.initials: L
authors.lastname: Lessard
authors.affiliation: Goodman Cancer Research Centre, McGill University, Montréal, Québec, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Aubry
authors.affiliation: Goodman Cancer Research Centre, McGill University, Montréal, Québec, Canada.
authors.forename: Eva
authors.initials: E
authors.lastname: Migon
authors.affiliation: Goodman Cancer Research Centre, McGill University, Montréal, Québec, Canada.
authors.forename: Jacinthe
authors.initials: J
authors.lastname: Sirois
authors.affiliation: Mammalian Functional Genetics Laboratory, Division of Blood Cancers, Australian Centre for Blood Diseases, Department of Clinical Haematology, Monash University and Alfred Health Alfred Centre, Melbourne, Victoria, Australia.
authors.forename: Jody J
authors.initials: JJ
authors.lastname: Haigh
authors.affiliation: Service d'anatomopathologie, Hôpital du Sacré-Cœur de Montréal, Montréal, Québec, Canada.
authors.forename: Louis R
authors.initials: LR
authors.lastname: Bégin
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
authors.forename: Lloyd C
authors.initials: LC
authors.lastname: Trotman
authors.affiliation: Faculté de Médecine Vétérinaire, Département de Pathologie et de Microbiologie, Université de Montréal, St-Hyacinthe, Québec, Canada.
authors.forename: Marilène
authors.initials: M
authors.lastname: Paquet
authors.affiliation: Goodman Cancer Research Centre, McGill University, Montréal, Québec, Canada. Division of Experimental Medicine, Department of Medicine, McGill University, Montréal, Québec, Canada. Department of Biochemistry, McGill University, Montréal, Québec, Canada. michel.tremblay@mcgill.ca.
authors.forename: Michel L
authors.initials: ML
authors.lastname: Tremblay
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D059305:Diet, High-Fat; D018450:Disease Progression; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D051059:PTEN Phosphohydrolase / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D007334:Insulin-Like Growth Factor I; D051057:Proto-Oncogene Proteins c-akt; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse