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[Cancer Research 59, 2516-2521, June 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 2516-2521, June 1, 1999]
© 1999 American Association for Cancer Research

Advances in Brief

Role of the Alternative INK4A Proteins in Human Keratinocyte Senescence: Evidence for the Specific Inactivation of p16INK4A upon Immortalization1

June Munro, Francesca J. Stott, Karen H. Vousden, Gordon Peters and E. Kenneth Parkinson2

Beatson Institute for Cancer Research, Cancer Research Campaign Beatson Laboratories, Glasgow G61 1BD, United Kingdom [J. M., E. K. P.]; Imperial Cancer Research Fund Laboratories, London WC2A 3PX, United Kingdom [F. J. S., G. P.]; and ABL Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201 [K. H. V.]

The INK4A locus on human chromosome 9p21 encodes two genes that have been implicated in replicative senescence and tumor suppression, p16INK4A and p14ARF. In contrast to p16INK4A, which is up-regulated to high levels, we were unable to detect p14ARF protein in senescent human keratinocytes. Also, p53, an established target of p14ARF, did not increase, suggesting that p14ARF is not instrumental in human keratinocyte senescence. In neoplastic keratinocyte cultures, p16INK4A inactivation was invariably associated with the immortal phenotype, and there was evidence for the inactivation of p16INK4A, independent of p14ARF, in 6 of 10 lines that lacked large homozygous deletions. In contrast, we failed to detect exon 1ß mutations or p16INK4A-independent deletions. These results emphasize the previously proposed role for p16INK4A in human keratinocyte senescence but do not rule out a supporting role for p14ARF inactivation.




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Copyright © 1999 by the American Association for Cancer Research.