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We hypothesized that p16 has a role in exit from cell cycle that becomes defective in cancer cells. Well characterized p16\u2010defective canine mammary cancer cell lines (CMT28, CMT27, and CMT12), derived stably p16\u2010transfected CMT cell clones (CMT27A, CMT27H, CMT28A, and CMT28F), and normal canine fibroblasts (NCF), were used to investigate expression of p16 after serum starvation into quiescence followed by re\u2010feeding to induce cell cycle re\u2010entry. The parental CMT cell lines used lack p16 expression either at the mRNA or protein expression levels, while p27 and other p16\u2010associated proteins, including CDK4, CDK6, cyclin D1, and Rb, were expressed. We have successfully demonstrated cell cycle arrest and relatively synchronous cell cycle re\u2010entry in parental CMT12, CMT28 and NCF cells as well as p16 transfected CMT27A, CMT27H, CMT28A, and CMT28F cells and confirmed this by<jats:sup>3<\/jats:sup>H\u2010thymidine incorporation and flow cytometric analysis of cell cycle phase distribution. p16\u2010transfected CMT27A and CMT27H cells exited cell cycle post\u2010serum\u2010starvation in contrast to parental CMT27 cells. NCF, CMT27A, and CMT28F cells expressed upregulated levels of p27 and p16 mRNA, post\u2010serum starvation, as cells exited cell cycle and entered quiescence. Because quiescence and differentiation are associated with increased levels of p27, our data demonstrating that p16 was upregulated along with p27 during quiescence, suggests a potential role for p16 in maintaining these non\u2010proliferative states. J. Cell. Biochem. 114: 1355\u20131363, 2013. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jcb.24476","type":"journal-article","created":{"date-parts":[[2012,12,13]],"date-time":"2012-12-13T14:07:09Z","timestamp":1355407629000},"page":"1355-1363","source":"Crossref","is-referenced-by-count":46,"title":["Tumor suppressor gene p16\/INK4A\/CDKN2A\u2010dependent regulation into and out of the cell cycle in a spontaneous canine model of breast cancer"],"prefix":"10.1002","volume":"114","author":[{"given":"Payal","family":"Agarwal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maninder","family":"Sandey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"DeInnocentes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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