PMID: 8959328Dec 1, 1996Paper

Up-regulation and functional role of p21Waf1/Cip1 during growth arrest of human breast carcinoma MCF-7 cells by phenylacetate

Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research
M GorospeN J Holbrook

Abstract

Phenylacetate (PA) and related aromatic fatty acids constitute a novel class of relatively nontoxic antineoplastic agents. These compounds induce tumor cytostasis and growth inhibition and differentiation of cancer cells, but little is known regarding the molecular events mediating these biological effects. Using human breast carcinoma MCF-7 cells as a model, we show here that PA-induced growth arrest is associated with enhanced expression of the cyclin-dependent kinase inhibitor p21Waf1/Cip1 and dephosphorylation of the retinoblastoma protein (pRB). The induction of p21WAF1/CIP1 mRNA by PA was independent of the cellular p53 status. To directly assess the contribution of p21Waf1/Cip1 to PA-mediated cytostasis, we compared the effects of PA in parental MCF-7 cells and cells expressing reduced levels of p21Waf1/Cip1 protein (clones AS.3 and AS.4), accomplished through constitutive expression of antisense p21Waf1/Cip1 transcripts. In contrast to parental cells, AS.3 and AS.4 cells did not show reduced pRB phosphorylation following PA treatment, indicating that p21Waf1/Cip1 induction by PA is required for dephosphorylation (inactivation) of pRB, a known mediator of cell cycle control. A prominent role for p21Waf1/Cip1 in mediating...Continue Reading

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