Cooperation of c-raf-1 and c-myc protooncogenes in the neoplastic transformation of simian virus 40 large tumor antigen-immortalized human bronchial epithelial cells

Journal Article · Thu Nov 30 23:00:00 EST 1989 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.86.24.10075· OSTI ID:6921545

Pfeifer, A M.A.; Mark, III, G E; Malan-Shibley, L; Amstad, P; Harris, C C ^[1]; Graziano, S ^[2]

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1. National Cancer Institute, Bethesda, MD (USA)
2. State Univ. of New York, Syracuse, NY (USA)

Overexpression of c-raf-1 and the myc family of protooncogenes is primarily associated with small cell carcinoma, which accounts for {approx} 25% of human lung cancer. To determine the functional significance of the c-raf-1 and/or c-myc gene expression in lung carcinogenesis and to delineate the relationship between protooncogene expression and tumor phenotype, the authors introduced both protooncogenes, alone or in combination, into human bronchial epithelial cells. Two retroviral recombinants, pZip-raf and pZip-myc, containing the complete coding sequences of the human c-raf-1 and murine c-myc genes, respectively, were constructed and transfected into simian virus 40 large tumor antigen-immortalized bronchial epithelial cells (BEAS-2B); this was followed by selection for G418 resistance. Cell lines established from tumors (designated RMT) revealed the presence of the cotransfected c-raf-1 and c-myc sequences and expressed morphological, chromosomal, and isoenzyme markers, which identified BEAS-2B cells as the progenitor line of the tumors. The data demonstrate that the concomitant expression of the c-raf and c-myc protooncogenes causes neoplastic transformation of human bronchial epithelial cells resulting in large cell carcinomas with certain neuroendocrine markers. The presented model system should be useful in studies of molecular events involved in multistage lung carcinogenesis.

• OSTI ID: 6921545
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 86:24; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANIMAL CELLS
ANIMAL TISSUES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
BRONCHI
CARBOXYLIC ACIDS
CARCINOMAS
CELL TRANSFORMATIONS
DAYS LIVING RADIOISOTOPES
DISEASES
DNA HYBRIDIZATION
DRUGS
ENZYME ACTIVITY
EPITHELIUM
EVEN-ODD NUCLEI
GENES
HYBRIDIZATION
ISOTOPES
LIGHT NUCLEI
LIPOTROPIC FACTORS
METHIONINE
MICROORGANISMS
NEOPLASMS
NUCLEI
ODD-ODD NUCLEI
ONCOGENES
ONCOGENIC TRANSFORMATIONS
ONCOGENIC VIRUSES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PARASITES
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
RADIOISOTOPES
RESPIRATORY SYSTEM
SULFUR 35
SULFUR ISOTOPES
TISSUES
TUMOR CELLS
VIRUSES