Studies of the progressive development of a malignant phenotype of a carcinogen initiated cell have been presented. For comparative purposes, stages in the progression have been identified where both carcinogen initiated cells and cells isolated from human squamous cell carcinoma (SCC) exhibit similar characteristics. Restrictions we faced in the past in the identification of cells in these stages have been overcome by the preparation of monoclonal antibodies (MoAb) that specifically identify these characteristics. These different MoAb's were prepared against specific cell surface antigens, phenotypic markers for normal cells, tumor cells, and keratin. Our current interest is to investigate how the tumor cells or carcinogen initiated cells progress from a normal phenotype to a malignant phenotype. Tumorigenicity, a natural endpoint for these studies, will be the stage of interest to investigate. We will: examine how the carcinogen initiated cells progress towards a neoplastic phenotype; isolate and separate tumor cell phenotypes that exhibit differences in cell surface antigens that are characteristic of changes in the cells as they progress from stage to stage; characterize the expression of intermediate keratin filaments in the tumor subpopulations that are in the different stages; prepare genomic DNA from tumor cell populations that exhibit LIG and tumorigenicity and compare the stages in the progression. A comparison of carcinogen initiated human epithelial cells with tumor cells with similar phenotypic characteristics will be undertaken using transfection technology and the progression from stage in the development of a malignant phenotype will be investigated. Moreover, an understanding of how malignant phenotypes lose specific cellular characteristics will be examined with molecular and specific phenotypic probes and the information gathered will aid us in understanding multistage carcinogenesis in a human model system.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA025907-08
Application #
3167064
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1979-07-01
Project End
1991-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
8
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Ohio State University
Department
Type
Schools of Medicine
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210
Crowe, D L; Milo, G E; Shuler, C F (1999) Keratin 19 downregulation by oral squamous cell carcinoma lines increases invasive potential. J Dent Res 78:1256-63
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Lee, H; Li, D; Prior, T et al. (1997) Ineffectiveness of the presence of H-ras/p53 combination of mutations in squamous cell carcinoma cells to induce a conversion of a nontumorigenic to a tumorigenic phenotype. Cell Biol Toxicol 13:419-34
Wani, G; Noyes, I; Milo, G E et al. (1997) Expression of molecular biomarkers in primary breast tumors implanted into a surrogate host: increased levels of cyclins correlate with tumor progression. Mol Med 3:273-83
Li, D; Yan, H; Chen, J et al. (1996) Malignant conversion of human cells by antisense cDNA to a putative tumor suppressor gene. Carcinogenesis 17:1751-5
Milo, G E; Li, D; Casto, B C et al. (1996) Malignant conversion of chemically transformed normal human cells. Proc Natl Acad Sci U S A 93:5229-34
Chen, J; Milo, G E; Shuler, C F et al. (1996) Xenograft growth and histodifferentiation of squamous cell carcinomas of the pharynx and larynx. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 81:197-202
Li, D; Noyes, I; Shuler, C et al. (1995) Cloning and sequencing of CATR1.3, a human gene associated with tumorigenic conversion. Proc Natl Acad Sci U S A 92:6409-13
Milo, G E; Shuler, C F; Lee, H et al. (1995) A conundrum in molecular toxicology: molecular and biological changes during neoplastic transformation of human cells. Cell Biol Toxicol 11:329-45
Milo, G E; Shuler, C F; Stoner, G et al. (1992) Conversion of premalignant human cells to tumorigenic cells by methylmethane sulfonate and methylnitronitrosoguanidine. Cell Biol Toxicol 8:193-205

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