Objectives of this project are (1) to establish and define a cell culture transformation system for identification of carcinogenic agents and humans at high risk for cancer; (2) to develop human cell transformation systems, with particular emphasis on epithelial cells. in order to study host factors regulating cell transformation and the mechanisms of carcinogenesis by chemicals, viruses, hormones and x-irradiation; and (3) to isolate and characterize oncogenes from human tumors. We have demonstrated (1) malignant transformation of immortalized human keratinocytes by an efficient polybrene-induced, DNA-mediated transfer of an activated human H-ras oncogene; (2) neoplastic transformation of immortalized human epidermal keratinocytes by exposure to x-ray irradiation; (3) malignant transformation of human primary epithelial cells by the cooperation of human papillomavirus type 16 and an activated ras oncogene and the enhancement of the transformation frequency by a glucocorticoid; (4) CR2, a cell surface membrane glycoprotein in an immortalized human keratinocyte line; (5) tpr-met oncogenic rearrangement in human tumor cell lines by polymerase chain reaction amplification of the transcript; (6) amplification, overexpression and rearrangement of the erbB-2 proto-oncogene in primary human stomach carcinomas.
