Characterization of mutant HA-ras gene expression in transformed murine keratinocyte lines grown under in vitro and in vivo conditions

Mol Carcinog. 1996 Dec;17(4):202-6. doi: 10.1002/(SICI)1098-2744(199612)17:4<202::AID-MC3>3.0.CO;2-F.

Abstract

We investigated the Ha-ras and Ki-ras gene status, tumorigenicity, pathology, line derivation, and intercellular communication of 7,12-dimethylbenz[a]anthracene-initiated papilloma-, carcinoma-, and hyperplastic skin-producing cell lines to further characterize them. Six of nine tumor cell lines grown in vitro expressed both mutant and normal Ha-ras proteins, and three lines expressed only normal Ha-ras. However, when grown subcutaneously in nude mice, seven of the nine lines expressed both mutant and normal Ha-ras, one line expressed normal Ha-ras, and one line did not grow subcutaneously. One papilloma line, P2/15, appeared to have an inducible mutant Ha-ras gene, as it was expressed only in vivo. These findings suggest that mutant Ha-ras genes may be lost in only a minor population of tumor lines during growth in culture. Finally, we found that mutant Ha-ras gene expression was strongly correlated with tumorigenicity in nude mice and that intercellular communication was strongly correlated with the derivation of the lines.

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene
  • Animals
  • Carcinogens
  • Carcinoma, Squamous Cell / chemically induced
  • Carcinoma, Squamous Cell / genetics
  • Cell Communication / physiology
  • Cell Division / physiology
  • Cell Line, Transformed
  • Gene Expression
  • Genes, ras*
  • Keratinocytes / drug effects
  • Keratinocytes / pathology*
  • Mice
  • Mice, Nude
  • Mutation*
  • Papilloma / genetics
  • Papilloma / metabolism
  • Papilloma / pathology
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology*
  • Tumor Cells, Cultured

Substances

  • Carcinogens
  • 9,10-Dimethyl-1,2-benzanthracene