The p53 status can influence the role of Sam68 in tumorigenesis.
The expression and activities of RNA binding proteins are frequently dysregulated in human cancer. Their roles, however, appears to be complex, with reports indicating both pro-tumorigenic and tumor suppressive functions. Here we show, using two classical mouse cancer models, that the role of KH-type RNA binding protein, Sam68, in tumor development can be influenced by the status of the p53 tumor suppressor. We demonstrate that in mice expressing wild type p53, Sam68-deficiency resulted in a higher incidence and malignancy of carcinogen-induced tumors, suggesting a tumor suppressive role for Sam68. In marked contrast, Sam68-haploinsufficiency significantly delayed the onset of tumors in mice lacking p53 and prolonged their survival, indicating that Sam68 accelerates the development of p53-deficient tumors. These findings provide considerable insight into a previously unknown relationship between Sam68 and the p53 tumor suppressor in tumorigenesis.
Terry Fox Molecular Oncology Group and the Bloomfield Center for Research on Aging, Sir Mortimer B Davis Jewish General Hospital, Lady Davis Institute for Medical Research, Montréal, Québec H3T 1E2, Canada.|Department of Medicine and Oncology, McGill University, Montréal, Québec H3A 1A1, Canada.
Naomi
N
Li
Terry Fox Molecular Oncology Group and the Bloomfield Center for Research on Aging, Sir Mortimer B Davis Jewish General Hospital, Lady Davis Institute for Medical Research, Montréal, Québec H3T 1E2, Canada.|Department of Medicine and Oncology, McGill University, Montréal, Québec H3A 1A1, Canada.
Chau Tuan-Anh
CT
Ngo
Department of Pathology, Jewish General Hospital, Montréal, Québec H3T 1E2, Canada.
Olga
O
Aleynikova
Department of Medicine and Oncology, McGill University, Montréal, Québec H3A 1A1, Canada.|Department of Biochemistry, McGill University, Montréal, Québec H3G 1Y6, Canada.|Rosalind and Morris Goodman Cancer Centre, Montréal, Québec H3A 1A3, Canada.
Nicole
N
Beauchemin
Terry Fox Molecular Oncology Group and the Bloomfield Center for Research on Aging, Sir Mortimer B Davis Jewish General Hospital, Lady Davis Institute for Medical Research, Montréal, Québec H3T 1E2, Canada.|Department of Medicine and Oncology, McGill University, Montréal, Québec H3A 1A1, Canada.
Stéphane
S
Richard
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D001397:Azoxymethane; D063646:Carcinogenesis; D057895:Haploinsufficiency; D051379:Mice; D008810:Mice, Inbred C57BL; D016601:RNA-Binding Proteins / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; C513253:Khdrbs1 protein, mouse; D016601:RNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D001397:Azoxymethane
RNA binding protein; Sam68; mouse models; p53; tumorigenesis
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