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 Woodworth, C. D.
Right arrow Articles by Iglesias, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Woodworth, C. D.
Right arrow Articles by Iglesias, M.

Cell Growth & Differentiation, Vol 7, Issue 6 811-820, Copyright © 1996 by American Association of Cancer Research


ARTICLES

Transforming growth factor beta 1 supports autonomous growth of human papillomavirus-immortalized cervical keratinocytes under conditions promoting squamous differentiation

CD Woodworth, J Chung, E McMullin, GD Plowman, S Simpson and M Iglesias
Laboratory of Biology, National Cancer Institute, Bethesda, Maryland 20892, USA. craigd@helix.nih.gov

Transforming growth factor beta (TGF-beta) inhibits proliferation of keratinocytes cultured from normal anogenital epithelia; however, human papillomavirus (HPV)-immortalized cell lines often exhibit increased resistance. Present results demonstrate that TGF-beta 1 (1-10 pM) stimulates growth of multiple HPV-immortalized cell lines when cultures are maintained under conditions promoting squamous differentiation (MCDB153-LB medium with 1.0 mM calcium and without epidermal growth factor and bovine pituitary extract). Growth stimulation by TGF-beta 1 was not due to altered expression of type I or II receptors, but was increased after extended passage of cells in culture. Differentiation of immortal keratinocytes resulted in induction of RNAs encoding two markers of squamous differentiation, involucrin and keratin 1, and decreased expression of RNAs for the epidermal growth factor (EGF) receptor and two ligands, amphiregulin and TGF-alpha. Growth stimulation by TGF-beta 1 occurred indirectly via establishment of an autocrine loop. TGF-beta 1 increased expression of RNAs encoding the EGF-R and amphiregulin, and also increased numbers of cell-surface EGF-Rs without altering their affinity. In contrast, TGF-beta 1 inhibited autonomous growth and transcription of amphiregulin RNA in normal keratinocytes. Growth stimulation by TGF-beta 1 could be blocked by a monoclonal antibody that competes for binding to the EGF-R or by a mixture of monoclonal antibodies that neutralize amphiregulin activity, confirming the importance of this autocrine pathway. Thus, partial abrogation of the growth inhibitory response to TGF-beta 1 sensitizes HPV-immortalized keratinocytes to a growth stimulatory signal mediated by an EGF-R-dependent pathway involving autocrine stimulation by amphiregulin.


This article has been cited by other articles:


Home page
J Mol EndocrinolHome page
Y.-H. Cheng, H. Utsunomiya, M. E. Pavone, P. Yin, and S. E. Bulun
Retinoic acid inhibits endometrial cancer cell growth via multiple genomic mechanisms
J. Mol. Endocrinol., March 23, 2011; 46(2): 139 - 153.
[Abstract] [Full Text] [PDF]


Home page
CVIHome page
M. Scott, M. Nakagawa, and A.-B. Moscicki
Cell-Mediated Immune Response to Human Papillomavirus Infection
Clin. Vaccine Immunol., March 1, 2001; 8(2): 209 - 220.
[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.