Characterization of mutant HA-ras gene expression in transformed murine keratinocyte lines grown under in vitro and in vivo conditions.
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.
Volpe
J P
JP
University of Texas M. D. Anderson Cancer Center, Science Park-Research Division, Smithville, USA.
Conti
C J
CJ
Slaga
T J
TJ
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002273:Carcinogens; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000235:genetics; D002450:Cell Communication / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002461:Cell Line, Transformed; D015870:Gene Expression; D011905:Genes, ras; D015603:Keratinocytes / Q000187:drug effects / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D010212:Papilloma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D014407:Tumor Cells, Cultured
D002273:Carcinogens; D015127:9,10-Dimethyl-1,2-benzanthracene