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 Munger, K.
Right arrow Articles by Moses, H. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Munger, K.
Right arrow Articles by Moses, H. L.

Cell Growth & Differentiation, Vol 3, Issue 5 291-298, Copyright © 1992 by American Association of Cancer Research


ARTICLES

Transforming growth factor beta 1 regulation of c-myc expression, pRB phosphorylation, and cell cycle progression in keratinocytes

K Munger, JA Pietenpol, MR Pittelkow, JT Holt and HL Moses
Laboratory of Tumor Virus Biology, National Cancer Institute, Bethesda, Maryland 20892.

Transforming growth factor beta 1 (TGF-beta 1) is a potent inhibitor of cellular proliferation in a variety of cell types, including skin keratinocytes. TGF-beta 1 suppression of c-myc transcription has been implicated in the mechanism of TGF-beta 1 inhibition of keratinocytes, and evidence suggests that the protein product of the retinoblastoma gene (pRB) is a necessary component in this pathway. Following growth factor stimulation of quiescent keratinocytes, TGF-beta 1 can inhibit cell cycle progression into S phase at any point prior to the G1-S transition but does not inhibit progression through the S phase of the cell cycle. Since pRB is hypophosphorylated during G1 and hyperphosphorylated during S and G2, the G1-S-specific phosphorylation of pRB becomes an attractive target for the growth-inhibitory activities of TGF-beta 1. However, in TGF-beta 1-treated primary human keratinocytes and in a series of human papilloma virus and SV40 immortalized human keratinocyte cell lines, the phosphorylation status of pRB strictly correlated with cell growth. No evidence was found for a direct effect of TGF-beta 1 on the phosphorylation state of pRB in these cells. It was further demonstrated that synthesis of c-myc protein can be rapidly inhibited by TGF-beta 1 addition throughout G1 and S phases, indicating that the phosphorylation state of pRB, at least as it varies during the cell cycle, does not alter the ability of TGF-beta 1 to suppress c-myc expression.(ABSTRACT TRUNCATED AT 250 WORDS)


This article has been cited by other articles:


Home page
J. Cell Sci.Home page
N. Ojeh, V. Pekovic, C. Jahoda, and A. Maatta
The MAGUK-family protein CASK is targeted to nuclei of the basal epidermis and controls keratinocyte proliferation
J. Cell Sci., August 15, 2008; 121(16): 2705 - 2717.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
B. K. Law, A. Chytil, N. Dumont, E. G. Hamilton, M. E. Waltner-Law, M. E. Aakre, C. Covington, and H. L. Moses
Rapamycin Potentiates Transforming Growth Factor {beta}-Induced Growth Arrest in Nontransformed, Oncogene-Transformed, and Human Cancer Cells
Mol. Cell. Biol., December 1, 2002; 22(23): 8184 - 8198.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
A. Glick, N. Popescu, V. Alexander, H. Ueno, E. Bottinger, and S. H. Yuspa
Defects in transforming growth factor-beta signaling cooperate with a Ras oncogene to cause rapid aneuploidy and malignant transformation of mouse keratinocytes
PNAS, December 21, 1999; 96(26): 14949 - 14954.
[Abstract] [Full Text] [PDF]


Home page
Cell Growth Differ.Home page
M. L. Rodriguez-Puebla, M. LaCava, and C. J. Conti
Cyclin D1 Overexpression in Mouse Epidermis Increases Cyclin-dependent Kinase Activity and Cell Proliferation in Vivo but Does Not Affect Skin Tumor Development
Cell Growth Differ., July 1, 1999; 10(7): 467 - 472.
[Abstract] [Full Text]


Home page
BloodHome page
R. A. Steinman, J. Huang, B. Yaroslavskiy, J. P. Goff, E. D. Ball, and A. Nguyen
Regulation of p21(WAF1) Expression During Normal Myeloid Differentiation
Blood, June 15, 1998; 91(12): 4531 - 4542.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
H. Kamesaki, K. Nishizawa, G. Y. Michaud, J. Cossman, and T. Kiyono
TGF-{beta}1 Induces the Cyclin-Dependent Kinase Inhibitor p27Kip1 mRNA and Protein in Murine B Cells
J. Immunol., January 15, 1998; 160(2): 770 - 777.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
K. F. Sachsenmeier, N. Sheibani, S. J. Schlosser, and B. L. Allen-Hoffmann
Transforming Growth Factor-1 Inhibits Nucleosomal Fragmentation in Human Keratinocytes following Loss of Adhesion
J. Biol. Chem., January 5, 1996; 271(1): 5 - 8.
[Abstract] [Full Text] [PDF]


Home page
Genes Dev.Home page
A J Wagner, J M Kokontis, and N Hay
Myc-mediated apoptosis requires wild-type p53 in a manner independent of cell cycle arrest and the ability of p53 to induce p21waf1/cip1.
Genes & Dev., December 1, 1994; 8(23): 2817 - 2830.
[Abstract] [PDF]


Home page
Genes Dev.Home page
A B Glick, M M Lee, N Darwiche, A B Kulkarni, S Karlsson, and S H Yuspa
Targeted deletion of the TGF-beta 1 gene causes rapid progression to squamous cell carcinoma.
Genes & Dev., October 15, 1994; 8(20): 2429 - 2440.
[Abstract] [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 © 1992 by the American Association of Cancer Research.