Open AccessMalignant transformation of mouse primary keratinocytes by Harvey sarcoma virus and its modulation by surrounding normal cells.
Author(s) -
G. Paolo Dotto,
Robert A. Weinberg,
Aurelio Ariza
Publication year - 1988
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.85.17.6389
Subject(s) - oncogene , malignant transformation , transformation (genetics) , fibroblast , phenotype , sarcoma , cancer research , keratinocyte , malignant cells , biology , chemistry , in vitro , microbiology and biotechnology , pathology , cell , cancer , medicine , cell cycle , biochemistry , gene , genetics
The activated ras oncogene that is present in Harvey sarcoma virus is able to induce malignant transformation of pure cultures of mouse primary keratinocytes. Malignant transformation of these cells is demonstrated by their ability to form carcinomas when grafted back onto syngeneic animals. However, expression of the malignant phenotype by the ras-transformed keratinocytes is drastically inhibited by the presence of normal dermal fibroblasts. This inhibitory effect depends on the ratio of fibroblasts to keratinocytes. It can be observed with mitomycin C-treated growth-arrested dermal fibroblasts and not with other cells, such as normal keratinocytes or established fibroblasts. Thus, a cellular environment approximating normal tissue can suppress tumor formation triggered by a single oncogene.