| A role for c-Abl in cell senescence and spontaneous immortalization. | |
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MedLine Citation:
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PMID: 22791394 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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c-Abl is a proto-oncogene that is essential for mouse development and tissue homeostasis. Misregulation of c-Abl, as seen in the constitutively active BCR-ABL, is the leading cause of human chronic myeloid leukemia. However, how the Abl proteins execute their functions still remains largely unknown. Here, we report an important role for c-Abl in replicative senescence and immortalization by regulating the expression of two tumor suppressors that induce cellular senescence, p53 and p16(INK4a). Using primary mouse embryonic fibroblasts (MEFs), we show that c-Abl ( -/- ) cells were more resistant to immortalization than wildtype cells using a standard 3T3 or 3T9 protocol. We could only immortalize three out of nine c-Abl ( -/- ) MEF cultures even when we increased the number of starting cells. This resistance was attributed to premature senescence and reduced survival in senescent c-Abl ( -/- ) cells due to an increase in p16(INK4a) and p53 expression. Deleting p53 allows c-Abl ( -/- ) p53 ( -/- ) MEFs to bypass senescence to be spontaneously immortalized. Cell immortalization, but not senescence, was generally accompanied by mutations in p53 in both wildtype and c-Abl ( -/- ) MEFs, although the spectrum is different from that of human tumors. The role for c-Abl in regulating cell senescence and immortalization might explain some of the developmental defects in c-Abl ( -/- ) mice and how BCR-ABL transforms cells. |
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Authors:
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Man Zhang; Lili Li; Zhongfeng Wang; Huijuan Liu; Junlin Hou; Min Zhang; Aijun Hao; Yun Liu; Guang He; Yongyong Shi; Lin He; Xueying Wang; Yue Wan; Baojie Li |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-7-13 |
Journal Detail:
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Title: Age (Dordrecht, Netherlands) Volume: - ISSN: 1574-4647 ISO Abbreviation: - Publication Date: 2012 Jul |
Date Detail:
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Created Date: 2012-7-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101250497 Medline TA: Age (Dordr) Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Clinical Laboratory, Beijing Shi Ji Tan Hospital, Capital Medical University, Beijing, People's Republic of China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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