Carcinogenesis, Vol. 20, No. 6, 921-926,
June 1999
© 1999 Oxford University Press
Commentary |
p16INK4a and the control of cellular proliferative life span
Children's Medical Research Institute, 214 Hawkesbury Rd, Westmead, Sydney, New South Wales 2145, Australia
Normal somatic cells have a limited proliferative capacity in vitro: after a finite number of cell divisions they eventually enter a non-proliferative state referred to as senescence. Senescence is thought to be a major tumor suppressor mechanism, and many cancers contain cells that have escaped from senescence and become immortalized. The role of telomerase activation in immortalization is currently attracting considerable attention, but immortalization is often associated with other changes including loss of normal function of the tumor suppressor locus, INK4a/ARF. Two proteins, p16INK4a and p14ARF, are encoded by this locus. Here we focus on p16INK4a and review accumulating evidence that loss of p16INK4a function may be involved in escape from the normal limits on cellular proliferative life span.
Abbreviations: cdk, cyclin-dependent kinase; HMEC, human mammary epithelial cells; HPV, human papillomavirus; LFS, Li–Fraumeni syndrome; MTS-1 gene, multiple tumor suppressor-1 gene; PD, population doubling; Rb, retinoblastoma; SV40, simian virus 40.
1 To whom correspondence should be addressed at: Children's Medical Research Institute, Locked Bag 23, Wentworthville, New South Wales 2145, Australia Email: rreddel{at}cmri.usyd.edu.au
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