Robert H. Rice1,2,3, Kathleen E. Steinmann4, Linda A. deGraffenried4, Qin Q1,2,3, Nicolas L. Taylor1,2,3, Richard Schlegel4
1Department of Environmental Toxicology, University of California, Davis, California 95616-8588; tDepartment of Molecular and Cellular Toxicology, Division of Biological Sciences,
2Harvard School of Public Health, Boston, Massachusetts 02115; and tCytogenetics Laboratory,
3UCD Medical Center, Sacramento, California 95816
4Department of Environmental Toxicology, University of California, Davis 95616-8588.
Tóm tắt
A human line of spontaneously immortalized keratinocytes (SIK cells) has been derived from ostensibly normal epidermis and has proven useful in dissecting molecular changes associated with immortalization. The original cultures had a normal karyotype and a colony forming efficiency of approximately 3% through 10 passages. At passage 15, after which normal strains ordinarily senesce, these cells continued vigorous growth and gradually increased in colony forming efficiency, stabilizing at approximately 30% by passage 40. During the early stage of increasing colony forming efficiency, the cells acquired a single i(6p) chromosomal aberration and 5- to 10-fold increases in expression of the cell-cycle control proteins cyclin A, cyclin B, and p34cdc2. Additional chromosomal aberrations accumulated at later passages (i(8q) and +7), but the i(6p) and the increased expression of cell-cycle proteins were maintained, raising the possibility that these features were important for immortalization. Regulation of cell growth and differentiation in the cultures appeared minimally altered compared with normal keratinocytes as judged by their microscopic appearance and generation of abortive colonies, sensitivity to growth suppression by transforming growth factor-beta and tetradecanoylphorbol acetate, and dependence upon epidermal growth factor for progressive growth.
