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p21 and p27: roles in carcinogenesis and drug resistance

Published online by Cambridge University Press:  01 July 2008

Abde M. Abukhdeir  and
Ben Ho Park
Abde M. Abukhdeir
Affiliation:
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Breast Cancer Research Program, Baltimore, MD, USA.
Ben Ho Park*
Affiliation:
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Breast Cancer Research Program, Baltimore, MD, USA.
*
*Corresponding author: Ben Ho Park, 1650 Orleans Street, CRBI, Room 1M42, Baltimore, MD 21231, USA. Tel: +1 410 502 7399; Fax: +1 410 614 8397; E-mail: [email protected]
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Abstract

Human cancers arise from an imbalance of cell growth and cell death. Key proteins that govern this balance are those that mediate the cell cycle. Several different molecular effectors have been identified that tightly regulate specific phases of the cell cycle, including cyclins, cyclin-dependent kinases (CDKs) and CDK inhibitors. Notably, loss of expression or function of two G1-checkpoint CDK inhibitors – p21 (CDKN1A) and p27 (CDKN1B) – has been implicated in the genesis or progression of many human malignancies. Additionally, there is a growing body of evidence suggesting that functional loss of p21 or p27 can mediate a drug-resistance phenotype. However, reports in the literature have also suggested p21 and p27 can promote tumours, indicating a paradoxical effect. Here, we review historic and recent studies of these two CDK inhibitors, including their identification, function, importance to carcinogenesis and finally their roles in drug resistance.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 10 , October 2008 , e19
Copyright
Copyright © Cambridge University Press 2008

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References

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The Reactome website is a curated knowledge base of biological pathways where readers can learn more about the cell cycle and other pathways:

Branzei, D. and Foiani, M. (2008) Regulation of DNA repair throughout the cell cycle. Nat Rev Mol Cell Biol 9, 297-308Google Scholar
Park, B.H. and Vogelstein, B. (2005) Tumor suppressor genes. In Cancer Medicine 7 (Kufe, D. et al. , eds), BC Decker, Hamilton Ontario, pp. 85-103Google Scholar
http://www.genomeknowledge.org/cgi-bin/frontpage?DB=gk_currentGoogle Scholar
http://www.sanger.ac.uk/genetics/CGP/cosmic/Google Scholar
Branzei, D. and Foiani, M. (2008) Regulation of DNA repair throughout the cell cycle. Nat Rev Mol Cell Biol 9, 297-308Google Scholar
Park, B.H. and Vogelstein, B. (2005) Tumor suppressor genes. In Cancer Medicine 7 (Kufe, D. et al. , eds), BC Decker, Hamilton Ontario, pp. 85-103Google Scholar
http://www.genomeknowledge.org/cgi-bin/frontpage?DB=gk_currentGoogle Scholar
http://www.sanger.ac.uk/genetics/CGP/cosmic/Google Scholar