CG&D
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gorospe, M.
Right arrow Articles by Holbrook, N. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gorospe, M.
Right arrow Articles by Holbrook, N. J.

Cell Growth & Differentiation, Vol 7, Issue 12 1609-1615, Copyright © 1996 by American Association of Cancer Research


ARTICLES

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

M Gorospe, S Shack, KZ Guyton, D Samid and NJ Holbrook
Laboratory of Cellular and Molecular Biology, Gerontology Research Center, National Institute on Aging, NIH, Baltimore, Maryland 21224, USA.

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 PA-induced growth arrest was further supported by the demonstration that embryonal fibroblasts derived from a p21WAF1/CIP1 knockout mouse (p21-/- mouse embryonal fibroblasts) did not growth arrest following PA treatment, whereas PA effectively induced p21WAF1/CIP1 mRNA and growth inhibition of the wild-type mouse embryonal fibroblasts. Taken together, our findings strongly support a role for p21Waf1/Cip1 in the PA-mediated inhibition of cell growth.


This article has been cited by other articles:


Home page
Molecular Cancer TherapeuticsHome page
C. Kennedy, K. Byth, C. L. Clarke, and A. deFazio
Cell Proliferation in the Normal Mouse Mammary Gland and Inhibition by Phenylbutyrate
Mol. Cancer Ther., October 1, 2002; 1(12): 1025 - 1033.
[Abstract] [Full Text] [PDF]


Home page
Molecular Cancer TherapeuticsHome page
A. L. Gartel and A. L. Tyner
The Role of the Cyclin-dependent Kinase Inhibitor p21 in Apoptosis
Mol. Cancer Ther., June 1, 2002; 1(8): 639 - 649.
[Abstract] [Full Text] [PDF]


Home page
Cell Growth Differ.Home page
B. A. Shin, K. Y. Ahn, H. Kook, J. T. Koh, I. C. Kang, H. C. Lee, and K. K. Kim
Overexpressed Human RAD50 Exhibits Cell Death in a p21WAF1/CIP1-dependent Manner: Its Potential Utility in Local Gene Therapy of Tumor
Cell Growth Differ., May 1, 2001; 12(5): 243 - 254.
[Abstract] [Full Text] [PDF]


Home page
Pharmacol. Rev.Home page
S. C. Dixon, K. B. Knopf, and W. D. Figg
The Control of Prostate-Specific Antigen Expression and Gene Regulation by Pharmacological Agents
Pharmacol. Rev., March 1, 2001; 53(1): 73 - 92.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
R. Pili, M. P. Kruszewski, B. W. Hager, J. Lantz, and M. A. Carducci
Combination of Phenylbutyrate and 13-cis Retinoic Acid Inhibits Prostate Tumor Growth and Angiogenesis
Cancer Res., February 1, 2001; 61(4): 1477 - 1485.
[Abstract] [Full Text]


Home page
Clin. Cancer Res.Home page
T. Davis, C. Kennedy, Y.-E. Chiew, C. L. Clarke, and A. deFazio
Histone Deacetylase Inhibitors Decrease Proliferation and Modulate Cell Cycle Gene Expression in Normal Mammary Epithelial Cells
Clin. Cancer Res., November 1, 2000; 6(11): 4334 - 4342.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
Y.-L. Chung, Y.-H. W. Lee, S.-H. Yen, and K.-H. Chi
A Novel Approach for Nasopharyngeal Carcinoma Treatment Uses Phenylbutyrate as a Protein Kinase C Modulator: Implications for Radiosensitization and EBV-targeted Therapy
Clin. Cancer Res., April 1, 2000; 6(4): 1452 - 1458.
[Abstract] [Full Text]


Home page
Clin. Cancer Res.Home page
D. Samid, M. Wells, M. E. Greene, W. Shen, C. N. A. Palmer, and A. Thibault
Peroxisome Proliferator-activated Receptor {{gamma}} as a Novel Target in Cancer Therapy: Binding and Activation by an Aromatic Fatty Acid with Clinical Antitumor Activity
Clin. Cancer Res., March 1, 2000; 6(3): 933 - 941.
[Abstract] [Full Text]


Home page
Clin. Cancer Res.Home page
T. E. Witzig, M. Timm, M. Stenson, P. A. Svingen, and S. H. Kaufmann
Induction of Apoptosis in Malignant B Cells by Phenylbutyrate or Phenylacetate in Combination with Chemotherapeutic Agents
Clin. Cancer Res., February 1, 2000; 6(2): 681 - 692.
[Abstract] [Full Text]


Home page
JCOHome page
S. M. Chang, J. G. Kuhn, H. I. Robins, S. C. Schold, A. M. Spence, M. S. Berger, M. P. Mehta, M. E. Bozik, I. Pollack, D. Schiff, et al.
Phase II Study of Phenylacetate in Patients With Recurrent Malignant Glioma: A North American Brain Tumor Consortium Report
J. Clin. Oncol., March 1, 1999; 17(3): 984 - 984.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1996 by the American Association of Cancer Research.