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Differential gene expression during multistage carcinogenesis

Journal Article · · Environmental Health Perspectives; (United States)
DOI:https://doi.org/10.1289/ehp.919351· OSTI ID:6094161
 [1];  [2]
  1. Univ. of Arizona Medical School, Tucson (United States)
  2. German Cancer Research Center, Heidelberg (West Germany)
The use of the mouse skin multistage model of carcinogenesis has aided our understanding of critical target genes in chemical carcinogenesis. The mutagenic activation of the Harvey-ras proto-oncogene has been found to be an early event associated with the initiation of mouse skin tumors by the polycyclic aromatic hydrocarbon 7,12 dimethylbenz(a)anthracene and the pure initiator ethyl carbamate (urethane). In contrast to chemical initiation of mouse skin tumors, ionizing radiation-initiated malignant skin tumors have been shown to possess distinct non-ras transforming gene(s). Differential screening of cDNA libraries made from chemically initiated malignant skin tumors has been used to identify a number of cellular gene transcripts that are overexpressed during mouse skin tumor progression. These differentially expressed genes include {beta}-actin, ubiquitin, a hyperproliferative keratin (K6), a gene whose product is a member of a fatty acid or lipid-binding protein family, and a gene called transin or stromelysin. The overexpression of the stromelysin gene, which encodes a metalloproteinase that degrades proteins in the basement membrane, is hypothesized to play a functional role in malignant tumor cell invasion and metastasis. The authors believe that the cloning, identification, and characterization of gene sequences that are differentially expressed during tumor progression could lead to the discovery of gene products that either play functional roles in skin tumor progression or in the maintenance of various progressive tumor phenotypes.
OSTI ID:
6094161
Journal Information:
Environmental Health Perspectives; (United States), Journal Name: Environmental Health Perspectives; (United States) Vol. 93; ISSN 0091-6765; ISSN EVHPA
Country of Publication:
United States
Language:
English