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.
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.
Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
A
A
Okamoto
W
W
Jiang
S J
SJ
Kim
E A
EA
Spillare
G D
GD
Stoner
I B
IB
Weinstein
C C
CC
Harris
D002453:Cell Cycle; D002460:Cell Line; D019938:Cyclin D1; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases; D016213:Cyclins / Q000378:metabolism*; D004847:Epithelial Cells; D004947:Esophagus / Q000166:cytology; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D015513:Oncogene Proteins / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016213:Cyclins; D015513:Oncogene Proteins; D018809:Proliferating Cell Nuclear Antigen; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D019938:Cyclin D1; D017346:Protein Serine-Threonine Kinases; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases