The purpose of this study is to investigate skin tumor progression by using markers which would permit the follow-up of tumors during different phases of skin carcinogenesis. Since the presence of gamma glutamyl transpeptidase (GGT) together with the decrease or absence of high molecular weight keratin polypeptides have been considered good markers of malignant potential in benign skin tumors, the sequential detection of these markers in tumors of different potentials produced by complete carcinogenesis, two-stage carcinogenesis and three-stage carcinogenesis will permit a detailed study of the malignant conversion of papillomas and keratoacanthomas. GGT will be studied using histochemical and biochemical techniques. The topohistochemical distribution of GGT, as well as the isoelectric focusing patterns, and the relationship of GGT with cell proliferation will be studied in the tumors produced by different protocols at different stages of tumor development. The keratin components will be studied in these same tumors using gel electrophoresis and immunohistochemical techniques. Other parameters which are useful in evaluating altered keratinocyte differentiation, such as filaggrin, plasminogen activator and lectin binding will also be studied in order to evaluate more completely the relationship between gradual altered differentiation patterns and skin tumor progression.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA044980-02
Application #
3187898
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1986-04-01
Project End
1988-01-31
Budget Start
1987-02-01
Budget End
1988-01-31
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Topeka Half-Way House
Department
Type
DUNS #
City
Topeka
State
KS
Country
United States
Zip Code
66606
Ruggeri, B A; Bauer, B; Zhang, S Y et al. (1994) Murine squamous cell carcinoma cell lines produced by a complete carcinogenesis protocol with benzo[a]pyrene exhibit characteristic p53 mutations and the absence of H-ras and cyl 1/cyclin D1 abnormalities. Carcinogenesis 15:1613-9
Klein-Szanto, A J; Ruggeri, B; Bianchi, A et al. (1993) Cellular and molecular changes during mouse skin tumor progression. Recent Results Cancer Res 128:193-204
Ruggeri, B; Caamano, J; Slaga, T J et al. (1992) Alterations in the expression of uvomorulin and Na+,K(+)-adenosine triphosphatase during mouse skin tumor progression. Am J Pathol 140:1179-85
Ruggeri, B; Caamano, J; Goodrow, T et al. (1991) Alterations of the p53 tumor suppressor gene during mouse skin tumor progression. Cancer Res 51:6615-21
Buchmann, A; Ruggeri, B; Klein-Szanto, A J et al. (1991) Progression of squamous carcinoma cells to spindle carcinomas of mouse skin is associated with an imbalance of H-ras alleles on chromosome 7. Cancer Res 51:4097-101
Chiba, M; Aldaz, C M; Conti, C J et al. (1991) Metastatic potential of mouse skin carcinomas produced by different protocols of chemical carcinogenesis. Invasion Metastasis 11:288-96
Klein-Szanto, A J (1991) The role of chemically induced epithelial hyperplasia in the development of human cancer. Prog Clin Biol Res 369:35-41
Bonfil, R D; Momiki, S; Conti, C J et al. (1989) Benzoyl peroxide enhances the invasive ability of a mouse epidermal carcinoma cell line. Int J Cancer 44:165-9
Klein-Szanto, A J; Larcher, F; Bonfil, R D et al. (1989) Multistage chemical carcinogenesis protocols produce spindle cell carcinomas of the mouse skin. Carcinogenesis 10:2169-72