A large body of evidence has accumulated that cancer occurs through a progression of multiple independent stages. Certain tissue culture cell lines have been used to identify genetic elements (oncogenes) which can induce a transition from a non-tumorigenic stage to one which is tumorigenic. Not all the genetic factors involved in malignant progression can be accounted for in terms of the expression of activated oncogenes. I have developed a human cell model in which stages of progression have been identified and can be used to study how oncogenes and potentially other genes are able to affect these changes. PA-1 human teratocarcinoma cells show progression as they are passaged in culture. Early passage cells are non-tumorigenic in athymic nude mice while late passage cells readily form tumors. This transition is induced by an activated N-ras oncogene. Metastatic PA-1 cells were derived from late passage tumor cells. Since all of these stages of PA-1 cell progression are essentially diploid, the progression cannot be accounted for by gross chromosomal aberrations. PA-1 cells provide a genetically stable model to analyze the molecular basis of malignant progression. I will employ multiple molecular biological approaches to identify the genetic elements which affect or are affected by the progression of malignancy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
3R01CA042810-01S1
Application #
3184386
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1987-07-01
Project End
1989-12-31
Budget Start
1987-07-01
Budget End
1987-12-31
Support Year
1
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Type
Hospitals
DUNS #
001910777
City
Houston
State
TX
Country
United States
Zip Code
77030
Hong, Y S; Kim, S Y; Bhattacharya, A et al. (1995) Structure and function of the HOX A1 human homeobox gene cDNA. Gene 159:209-14
Kannan, P; Buettner, R; Chiao, P J et al. (1994) N-ras oncogene causes AP-2 transcriptional self-interference, which leads to transformation. Genes Dev 8:1258-69
Buettner, R; Kannan, P; Imhof, A et al. (1993) An alternatively spliced mRNA from the AP-2 gene encodes a negative regulator of transcriptional activation by AP-2. Mol Cell Biol 13:4174-85
Shin, D M; Chiao, P J; Sacks, P G et al. (1993) Activation of ribosomal protein S2 gene expression in a hamster model of chemically induced oral carcinogenesis. Carcinogenesis 14:163-6
Chiao, P J; Shin, D M; Sacks, P G et al. (1992) Elevated expression of the ribosomal protein S2 gene in human tumors. Mol Carcinog 5:219-31
Mukhopadhyay, T; Tainsky, M; Cavender, A C et al. (1991) Specific inhibition of K-ras expression and tumorigenicity of lung cancer cells by antisense RNA. Cancer Res 51:1744-8
Bischoff, F Z; Strong, L C; Yim, S O et al. (1991) Tumorigenic transformation of spontaneously immortalized fibroblasts from patients with a familial cancer syndrome. Oncogene 6:183-6
Chiao, P J; Kannan, P; Yim, S O et al. (1991) Susceptibility to ras oncogene transformation is coregulated with signal transduction through growth factor receptors. Oncogene 6:713-20
Buettner, R; Yim, S O; Hong, Y S et al. (1991) Alteration of homeobox gene expression by N-ras transformation of PA-1 human teratocarcinoma cells. Mol Cell Biol 11:3573-83
Kannan, P; Buettner, R; Pratt, D R et al. (1991) Identification of a retinoic acid-inducible endogenous retroviral transcript in the human teratocarcinoma-derived cell line PA-1. J Virol 65:6343-8

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