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PMID: 7972105 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Overexpression of human cyclin D1 reduces the transforming growth factor beta (TGF-beta) type II receptor and growth inhibition by TGF-beta 1 in an immortalized human esophageal epithelial cell line.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 91 ·No. 24 ·1994-11-22 ·Pages 11576-80

Okamoto A, Jiang W, Kim SJ, Spillare EA, Stoner GD, Weinstein IB, Harris CC

Abstract

Cyclin D1 has been implicated in G1 cell cycle progression and is frequently amplified, overtranscribed, and oversynthesized in human tumors, including esophageal carcinomas. To further address the role of cyclin D1 in cell cycle control and tumorigenesis, we have stably transfected the human cyclin D1 in the nontumorigenic esophageal epithelial cell line HET-1A. These transfected cells, which express increased amounts of cyclin D1, have enhanced colony-forming efficiency and saturation density and are resistant to growth inhibition by TGF-beta 1 compared with the parental cell line or a control vector cell clone. The clones which express increased amounts of cyclin D1 exhibited a decrease in the amount of TGF-beta type II receptor, indicating a plausible mechanism for their diminished response to TGF-beta 1. Therefore, deregulated expression of the cyclin D1 gene can modulate the negative growth factor pathway of TGF-beta 1 and may disturb the control of epithelial cell proliferation in esophageal carcinogenesis.

MeSH Terms
Cell Cycle Cell Line Cyclin D1 Cyclin-Dependent Kinase 4 Cyclin-Dependent Kinases Cyclins/metabolism Epithelial Cells Esophagus/cytology Gene Expression Humans In Vitro Techniques Oncogene Proteins/metabolism Proliferating Cell Nuclear Antigen/metabolism Protein Serine-Threonine Kinases/metabolism Proto-Oncogene Proteins RNA, Messenger/genetics Receptors, Transforming Growth Factor beta/metabolism Transforming Growth Factor beta/pharmacology
Chemicals
Cyclins Oncogene Proteins Proliferating Cell Nuclear Antigen Proto-Oncogene Proteins RNA, Messenger Receptors, Transforming Growth Factor beta Transforming Growth Factor beta Cyclin D1 Protein Serine-Threonine Kinases CDK4 protein, human Cyclin-Dependent Kinase 4 Cyclin-Dependent Kinases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Okamoto A
Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Jiang W
Kim S J
Spillare E A
Stoner G D
Weinstein I B
Harris C C
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.91.24.11576
Published
1994-11-22
Pages
11576-80
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC45274
Subset
IM
Grants
NCI NIH HHS · CA02111 · United States
External Links
PubMed source DOI: 10.1073/pnas.91.24.11576 PMC Full Text View journal details
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