Biomaterial Database

Transforming growth factor-beta 1 (TGF beta 1) enhances apoptosis in human papillomavirus type 16-immortalized human ectocervical epithelial cells. 1995

E A Rorke, and J W Jacobberger

Department of Environmental Health Sciences, Case Western Reserve University, Cleveland, Ohio 44106.

Transforming growth factor beta (TGF beta) is a potent inhibitor of epithelial cell growth. In the present study TGF beta 1 modulation of human ectocervical epithelial cell growth and differentiation is evaluated using an HPV16-immortalized human ectocervical cell line, ECE16-1. These cells were found to contain a high-affinity receptor for TGF beta 1 (Kd = 75 pM). TGF beta (10-500 pg/ml) suppressed ECE16-1 growth and [3H]thymidine incorporation in a dose-dependent manner. Growth inhibition was reversible at TGF beta 1 concentrations of 100 pg/ml or less. At higher concentrations of TGF beta 1, treatment for longer than 2 days induced irreversible growth inhibition. In addition to its effects on cell growth, TGF beta 1 treatment increased apoptosis in ECE16-1 cells as measured by an increase in cornified envelope formation, flow cytometry, and DNA fragmentation. Apoptosis was enhanced at doses > or = 100 pg/ml. There was a highly significant increase in the activity of tissue transglutaminase, an enzyme believed to play an important role in apoptosis. This increase in transglutaminase activity was paralleled by a TGF beta 1-stimulated increase in fibronectin levels. Transglutaminase and fibronectin have been shown to associate during tissue remodeling. These data suggest that TGF beta 1 may act as an important paracrine/autocrine factor to stimulate normal cervical remodeling and to limit HPV16-immortalized cervical cell progression by stimulating apoptosis. The induction of fibronectin and tissue transglutaminase suggests that the TGF beta 1 pathway of cell death differs from that of normal ectocervical epithelial cell differentiation, which is mediated by epidermal transglutaminase.

UI	MeSH Term	Description	Entries
D007633	Keratins	A class of fibrous proteins or scleroproteins that represents the principal constituent of EPIDERMIS; HAIR; NAILS; horny tissues, and the organic matrix of tooth ENAMEL. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms a coiled-coil alpha helical structure consisting of TYPE I KERATIN and a TYPE II KERATIN, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. alpha-Keratins have been classified into at least 20 subtypes. In addition multiple isoforms of subtypes have been found which may be due to GENE DUPLICATION.	Cytokeratin,Keratin Associated Protein,Keratin,Keratin-Associated Proteins,alpha-Keratin,Associated Protein, Keratin,Keratin Associated Proteins,Protein, Keratin Associated,alpha Keratin
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D011503	Transglutaminases	Transglutaminases catalyze cross-linking of proteins at a GLUTAMINE in one chain with LYSINE in another chain. They include keratinocyte transglutaminase (TGM1 or TGK), tissue transglutaminase (TGM2 or TGC), plasma transglutaminase involved with coagulation (FACTOR XIII and FACTOR XIIIa), hair follicle transglutaminase, and prostate transglutaminase. Although structures differ, they share an active site (YGQCW) and strict CALCIUM dependence.	Glutaminyl-Peptide Gamma-Glutamyltransferases,Protein-Glutamine gamma-Glutamyltransferases,Transglutaminase,Gamma-Glutamyltransferases, Glutaminyl-Peptide,Glutaminyl Peptide Gamma Glutamyltransferases,Protein Glutamine gamma Glutamyltransferases,gamma-Glutamyltransferases, Protein-Glutamine
D002454	Cell Differentiation	Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.	Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002455	Cell Division	The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.	M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D002461	Cell Line, Transformed	Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.	Transformed Cell Line,Cell Lines, Transformed,Transformed Cell Lines
D002584	Cervix Uteri	The neck portion of the UTERUS between the lower isthmus and the VAGINA forming the cervical canal.	Cervical Canal of the Uterus,Cervical Canal, Uterine,Ectocervix,Endocervical Canal,Endocervix,External Os Cervix,External Os of the Cervix,Uterine Cervical Canal,Cervix,Cervixes,Uterine Cervix,Canal, Endocervical,Canal, Uterine Cervical,Cervix, External Os,Cervix, Uterine,Endocervical Canals,Uterine Cervical Canals
D004247	DNA	A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).	DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004847	Epithelial Cells	Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.	Adenomatous Epithelial Cells,Columnar Glandular Epithelial Cells,Cuboidal Glandular Epithelial Cells,Glandular Epithelial Cells,Squamous Cells,Squamous Epithelial Cells,Transitional Epithelial Cells,Adenomatous Epithelial Cell,Cell, Adenomatous Epithelial,Cell, Epithelial,Cell, Glandular Epithelial,Cell, Squamous,Cell, Squamous Epithelial,Cell, Transitional Epithelial,Cells, Adenomatous Epithelial,Cells, Epithelial,Cells, Glandular Epithelial,Cells, Squamous,Cells, Squamous Epithelial,Cells, Transitional Epithelial,Epithelial Cell,Epithelial Cell, Adenomatous,Epithelial Cell, Glandular,Epithelial Cell, Squamous,Epithelial Cell, Transitional,Epithelial Cells, Adenomatous,Epithelial Cells, Glandular,Epithelial Cells, Squamous,Epithelial Cells, Transitional,Glandular Epithelial Cell,Squamous Cell,Squamous Epithelial Cell,Transitional Epithelial Cell
D005260	Female		Females