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An Opposite Effect of the CDK Inhibitor, p18<sup>INK4c</sup> on Embryonic Stem Cells Compared with Tumor and Adult Stem Cells

Li, Y and Pal, R and Sung, LY and Feng, H and Miao, W and Cheng, SY and Tian, C and Cheng, T (2012) An Opposite Effect of the CDK Inhibitor, p18<sup>INK4c</sup> on Embryonic Stem Cells Compared with Tumor and Adult Stem Cells. PLoS ONE, 7 (9).

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Abstract

Self-renewal is a feature common to both adult and embryonic stem (ES) cells, as well as tumor stem cells (TSCs). The cyclin-dependent kinase inhibitor, p18INK4c, is a known tumor suppressor that can inhibit self-renewal of tumor cells or adult stem cells. Here, we demonstrate an opposite effect of p18 on ES cells in comparison with teratoma cells. Our results unexpectedly showed that overexpression of p18 accelerated the growth of mouse ES cells and embryonic bodies (EB); on the contrary, inhibited the growth of late stage teratoma. Up-regulation of ES cell markers (i.e., Oct4, Nanog, Sox2, and Rex1) were detected in both ES and EB cells, while concomitant down-regulation of various differentiation markers was observed in EB cells. These results demonstrate that p18 has an opposite effect on ES cells as compared with tumor cells and adult stem cells. Mechanistically, expression of CDK4 was significantly increased with overexpression of p18 in ES cells, likely leading to a release of CDK2 from the inhibition by p21 and p27. As a result, self-renewal of ES cells was enhanced. Our current study suggests that targeting p18 in different cell types may yield different outcomes, thereby having implications for therapeutic manipulations of cell cycle machinery in stem cells. © 2012 Li et al.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Li, Y
Pal, R
Sung, LY
Feng, H
Miao, W
Cheng, SY
Tian, C
Cheng, T
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorAkagi, TadayukiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, Offices, or Units > Pittsburgh Cancer Institute
Date: 26 September 2012
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 7
Number: 9
DOI or Unique Handle: 10.1371/journal.pone.0045212
Schools and Programs: School of Medicine > Pathology
School of Medicine > Radiation Oncology
Refereed: Yes
Other ID: NLM PMC3458833
PubMed Central ID: PMC3458833
PubMed ID: 23049777
Date Deposited: 30 Oct 2012 19:19
Last Modified: 22 Jun 2021 13:55
URI: http://d-scholarship.pitt.edu/id/eprint/16051

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