Control of growth and squamous differentiation in normal human bronchial epithelial cells by chemical and biological modifiers and transferred genes

Journal Article · Wed Mar 01 04:00:00 EST 1989 · Environ. Health Perspect.; (United States)

DOI:https://doi.org/10.1289/ehp.8980209· OSTI ID:6096241

Pfeifer, A M; Lechner, J F; Masui, T; Reddel, R R; Mark, G E; Harris, C C

The majority of human lung cancers arise from bronchial epithelial cells. The normal pseudostratified bronchial epithelium is composed of basal, mucous, and ciliated cells. This multi-differentiated epithelium usually responds to xenobiotics and physical injury by undergoing basal cell hyperplasia, mucous cell hyperplasia, and squamous metaplasia. One step of the multistage process of carcinogenesis is thought to involve aberrations in control of the squamous metaplastic processes. Decreased responsiveness to regulators of terminal squamous differentiation may confer a selective clonal expansion advantage to an initiated cell. We studied the effects of endogenous (e.g., transforming growth factor beta 1 (TGF-beta 1) and serum) and exogenous (e.g., 12-O-tetradecanoyl-13-phorbol-acetate (TPA), tobacco smoke condensate, and aldehydes) modifiers of normal human bronchial epithelial (NHBE) cell in a serum-free culture system. NHBE cells are growth inhibited by all of these compounds and induced to undergo squamous differentiation by TGF-beta 1 or TPA. In contrast, lung carcinoma cell lines are relatively resistant to inducers of terminal squamous differentiation which may provide them with a selective growth advantage. Chemical agents and activated protooncogenes (ras,raf,myc) altered the response to endogenous and exogenous inducers of squamous differentiation and caused extended cellular lifespan, aneuploidy, and/or tumorigenicity. The data suggest a close relationship between dysregulation of terminal differentiation pathways and neoplastic transformation of human bronchial epithelial cells.

• Research Organization: National Cancer Institute, Bethesda, MD (USA)
• OSTI ID: 6096241
• Journal Information: Environ. Health Perspect.; (United States), Journal Name: Environ. Health Perspect.; (United States) Vol. 80; ISSN EVHPA
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AEROSOLS
ALDEHYDES
AMP
ANIMAL CELLS
ANIMAL TISSUES
BIOLOGICAL EFFECTS
BODY
BRONCHI
CARCINOGENS
CELL CULTURES
CELL DIFFERENTIATION
COLLOIDS
DISPERSIONS
EPITHELIUM
ESTERS
GENES
IN VITRO
NUCLEOTIDES
ONCOGENES
ORGANIC COMPOUNDS
PHORBOL ESTERS
RESIDUES
RESPIRATORY SYSTEM
SMOKES
SOLS
TISSUES
TOBACCO SMOKES
TOXICITY