The malignant conversion step of mouse skin carcinogenesis
- National Cancer Institute, Bethesda, MD (USA)
Multiple benign squamous papillomas commonly precede the development of an occasional squamous cell carcinoma in mouse skin carcinogenesis. The incidence of carcinomas can be enhanced by treating papilloma-bearing mice with mutagens such as urethane, nitroquinoline-N-oxide, or cisplatinum. This observation suggests that a genetic change is required for malignant conversion. The malignant phenotype is characterized by a marked reduction in the transcription of specific epidermal differentiation markers, a pattern which is useful for the early diagnosis of malignant conversion. Cells expressing a benign phenotype can be obtained by introducing the v-ras{sup Ha} oncogene into cultured epidermal cells by a replication-defective retrovirus. Alternatively, benign tumor cells can be cultured from papillomas induced by chemical carcinogens in vivo or from carcinogen-treated mouse epidermis. In all cases, the benign phenotype in vitro is characterized by an altered biological response to changes in extracellular calcium, an important determinant of the differentiation state of cultured normal keratinocytes. Transfection of cloned plasmid DNA into benign tumor cells has revealed that transforming constructs of the fos oncogene induce malignant conversion, whereas myc and adenovirus E1A oncogenes do not. Cultured normal epidermal cells, exposed to the v-ras and the v-fos oncogenes simultaneously, are malignantly transformed. Alone, the fos oncogene does not detectably alter the phenotype of normal keratinocytes. These studies indicate that a limited number of genes is involved in epidermal carcinogenesis.
- OSTI ID:
- 5624296
- Journal Information:
- Environmental Health Perspectives; (USA), Journal Name: Environmental Health Perspectives; (USA) Vol. 88; ISSN 0091-6765; ISSN EVHPA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
AROMATICS
AZAARENES
AZINES
BIOLOGICAL MARKERS
BODY
CARBAMATES
CARBONIC ACID DERIVATIVES
CARBOXYLIC ACID SALTS
CARCINOGENESIS
CARCINOMAS
CELL DIFFERENTIATION
DISEASES
GENES
HETEROCYCLIC COMPOUNDS
MAMMALS
MICE
MOLECULAR BIOLOGY
NEOPLASMS
NITRO COMPOUNDS
ONCOGENES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PATHOGENESIS
PHENOTYPE
PLATINUM COMPOUNDS
PYRIDINES
QUINOLINES
RODENTS
SKIN
TRANSCRIPTION
TRANSITION ELEMENT COMPOUNDS
TUMOR CELLS
URETHANE
VERTEBRATES