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- Title
Spontaneous Immortalization of Human Epidermal Cells with Naturally Elevated Telomerase.
- Authors
Rea, Miguel A.; Lei Zhou; Qin Qin; Barrandon, Yann; Easley, Karen W.; Gungner, Sarah F.; Phillips, Marjorie A.; Holland, William S.; Gumerlock, Paul H.; Rocke, David M.; Rice, Robert H.
- Abstract
This work explores spontaneous immortalization in keratinocytes, derived from two skin samples, that display naturally elevated telomerase activity. Serially passaged with 3T3 feeder layer support, the keratinocytes were examined for colony-forming ability, telomerase activity, telomere length, and finally gene expression using Affymetrix DNA microarrays. The cells initially exhibited normal karyotypes and low colony-forming efficiencies typical of normal epidermal cells, but after 40 passages (≈400 generations) colony-forming ability increased markedly, yielding immortalized lines exhibiting a small number of chromosomal aberrations and functionally normal p53. An improved protocol for analysis of microarray data permitted detection of 707 transcriptional changes accompanying immortalization including reduced p16INK4A mRNA. Telomerase activity was clearly elevated in cells even at low passage from both samples, and telomerase catalytic subunit mRNA was greatly elevated in those with elevated colony-forming ability. The data raise the possibility of an unusual natural phenotype in which aberrant telomerase regulation extends keratinocyte lifespan until rare variants evade senescence. In addition to revealing a potential tumor-prone syndrome, the findings emphasize the desirability of carefully minimizing the degree or timing of elevated expression of telomerase used to immortalize cells for therapeutic purposes.Journal of Investigative Dermatology (2006) 126, 2507–2515. doi:10.1038/sj.jid.5700424; published online 15 June 2006
- Subjects
KERATINOCYTES; TELOMERASE; GENE expression; DNA microarrays; MESSENGER RNA; PHENOTYPES
- Publication
Journal of Investigative Dermatology, 2006, Vol 126, Issue 11, p2507
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1038/sj.jid.5700424