The design of model systems of chemical carcinogenes has been extremely useful in advancing the understanding of the mechanisms of tumorigenesis. We have been using the polycyclic aromatic hydrocarbon DMBA to induce in rabbits the formation of skin tumors. A protocol was utilized to obtain a particular type of tumor, keratoacanthoma, that is benign and self-regressing. This proposal approaches the less frequently studied field of benign tumors with the added interesting point of looking into a tumor regression process. Already completed work has identified activated H-ras as an important component of this system and using a combination of pathology, molecular biology and immunohistochemistry the different phases of this tumor system will be investigated. Using PCR amplification and oligonucleotide hybridization the early stages of tumor development will be analyzed as well as the progression from keratoacanthoma to squamous cell carcinoma. Parallel studies with samples from human keratoacanthoma will be undertaken to correlate them with the animal studies. The role of the H-ras oncogene in the process of tumor regression will be studied in great detail making use of specific antibodies for the mutant protein. To complete the analysis of the regression process, retinoids and TGF beta, agents of epithelial differentiation will be introduced in the system to study their correlation with H-ras oncogene expression. The study of this benign and self-regressing tumor in both humans and the rabbit DMBA induced model should provide important information on the role of ras oncogenes in the different stages of tumorigenesis.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA050434-01
Application #
3194897
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1989-08-01
Project End
1992-07-31
Budget Start
1989-08-01
Budget End
1990-07-31
Support Year
1
Fiscal Year
1989
Total Cost
Indirect Cost
Name
New York University
Department
Type
Schools of Medicine
DUNS #
004514360
City
New York
State
NY
Country
United States
Zip Code
10012
Osei-Sarfo, Kwame; de Castro, Ignacio Perez; Pellicer, Angel (2012) p15(INK4b) plays a crucial role in murine lymphoid development and tumorigenesis. Carcinogenesis 33:708-13
Suzme, R; Tseng, J-C; Levin, B et al. (2012) Sindbis viral vectors target hematopoietic malignant cells. Cancer Gene Ther 19:757-66
Osei-Sarfo, K; Martello, L; Ibrahim, S et al. (2011) The human Rgr oncogene is overexpressed in T-cell malignancies and induces transformation by acting as a GEF for Ras and Ral. Oncogene 30:3661-71
Martello, Laura A; Pellicer, Angel (2006) Biochemical and biological analyses of Rgr RalGEF oncogene. Methods Enzymol 407:115-28
Jimenez, Maria; Perez de Castro, Ignacio; Benet, Marta et al. (2004) The Rgr oncogene induces tumorigenesis in transgenic mice. Cancer Res 64:6041-9
Perez de Castro, Ignacio; Bivona, Trever G; Philips, Mark R et al. (2004) Ras activation in Jurkat T cells following low-grade stimulation of the T-cell receptor is specific to N-Ras and occurs only on the Golgi apparatus. Mol Cell Biol 24:3485-96
Hernandez-Munoz, Inmaculada; Benet, Marta; Calero, Miguel et al. (2003) rgr oncogene: activation by elimination of translational controls and mislocalization. Cancer Res 63:4188-95
Leonardi, Peter; Kassin, Ezra; Hernandez-Munoz, Inmaculada et al. (2002) Human rgr: transforming activity and alteration in T-cell malignancies. Oncogene 21:5108-16
Zagzag, D; Miller, D C; Knopp, E et al. (2000) Primitive neuroectodermal tumors of the brainstem: investigation of seven cases. Pediatrics 106:1045-53
Hernandez-Munoz, I; Malumbres, M; Leonardi, P et al. (2000) The Rgr oncogene (homologous to RalGDS) induces transformation and gene expression by activating Ras, Ral and Rho mediated pathways. Oncogene 19:2745-57

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