| First Author | Paramio JM | Year | 2001 |
| Journal | J Biol Chem | Volume | 276 |
| Issue | 47 | Pages | 44203-11 |
| PubMed ID | 11551927 | Mgi Jnum | J:72780 |
| Mgi Id | MGI:2153591 | Doi | 10.1074/jbc.M105650200 |
| Citation | Paramio JM, et al. (2001) The ink4a/arf Tumor Suppressors Cooperate with p21cip1/waf in the Processes of Mouse Epidermal Differentiation, Senescence, and Carcinogenesis. J Biol Chem 276(47):44203-11 |
| abstractText | In mammalian cells, cell cycle withdrawal is a prerequisite for terminal differentiation. Accordingly, in most tissues, including epidermis, the expression of the cyclin-dependent kinase inhibitors increases during differentiation. However, the actual role of cyclin-dependent kinase inhibitors is unclear. Different aspects of epidermal growth and differentiation in ink4a(Delta2,3)-null, p21-null, and ink4a(Delta2,3)/p21-doubly deficient mice were studied. Altered differentiation and decreased age-related senescence were found in the epidermis of ink4a(Delta2,3)/p21-null mice and, to a lesser extent, in ink4a(Delta2,3)- and p21-null mice. ink4a(Delta2,3)/p21-null primary keratinocytes underwent cell cycle arrest upon calcium or transforming growth factor-beta treatment, but failed to differentiate. This differentiation deficiency was not observed in p21- or ink4a(Delta2,3)-deficient keratinocytes. Upon infection with a v-Ha-ras-coding retrovirus, wild-type keratinocytes displayed features indicative of premature cell senescence. In p21- or ink4a(Delta2,3)-deficient keratinocytes, only a partial response was observed. ink4a(Delta2,3)/p21-deficient keratinocytes did not display senescent features, but showed increased tumorigenic potential upon injection into nude mice. These results indicate that ink4a/arf and cip1/waf genes cooperate to allow normal keratinocyte differentiation and that the absence of both favors malignant transformation. |
