Cambridge Journals Online

Review Article

p21 and p27: roles in carcinogenesis and drug resistance

Abde M. Abukhdeira1 and Ben Ho Parka1 c1 a1 The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Breast Cancer Research Program, Baltimore, MD, USA.

Article author query abukhdeir am   park bh

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.

Correspondence:

^c1 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: bpark2@jhmi.edu