This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, Q. Articles by Hakura, A. Search for Related Content PubMed PubMed Citation Articles by Li, Q. Articles by Hakura, A.

Abrogation of c-kit/Steel factor-dependent Tumorigenesis by Kinase Defective Mutants of the C-kit Receptor: c-kit Kinase Defective Mutants as Candidate Tools for Cancer Gene Therapy¹

Research Institute for Microbial Diseases [Q. L., Y. N., A. H.] and Genome Information Research Center [G. K.]. Osaka University, 3-1 Yamadaoka, Suita, Osaka 565, and Department of Pathology, Minoo Municipal Hospital, 5-7-1 Kayano, Minoo. Osaka 562 [S. I.]. Japan

The growth and survival of many types of cancer cells are known to be supported by specific growth factor/cytokine systems. Among these, the activation of c-kit receptor and its ligand steel factor participates in several types of human carcinogenesis. W mutations of laboratory mouse strains are loss of functional mutations of the c-kit receptor. To examine the validity of these mutants in investigating c-kit-mediated carcinogenesis and in the treatment of c-kit-dependent tumors, we introduced various W mutations (W, W^v, and W⁴²) into a transgenic mouse strain carrying human papillomavirus oncogenes, in which c-kit/Steel-mediated tumorigenesis occurs with a very high incidence. In all transgenic strains carrying a W mutation, the c-kit deficiency affected the tumorgenic process to various degrees. Tumor development was markedly suppressed in transgenic strains carrying kinase defective mutations (W^v and W⁴²) in a heterozygous condition. In null-type (W) heterozygous transgenic mice, tumorigenesis was suppressed at a lower level. Moreover, minimal focal legions or, in some cases, no focal legions were found in the testes of W/W^v heterozygous transgenic mice, showing a close relationship between tumor cell growth and the degree of c-kit inactivation. These results indicated that c-kit activity is a pivotal determinant of testicular tumor development and that the kinase defective mutants of c-kit are valuable for treating c-kit-dependent cancer, as well as for clarifying the c-kit-mediated carcinogenesis.

¹ This work was supported by grants from the Ministry of Education, Science, Sports and Culture of Japan.

² To whom requests for reprints should be addressed.

Received 7/22/96. Accepted 8/16/96.

This article has been cited by other articles:

				J. R. Caceres-Cortes, J. A. Alvarado-Moreno, K. Waga, R. Rangel-Corona, A. Monroy-Garcia, L. Rocha-Zavaleta, J. Urdiales-Ramos, B. Weiss-Steider, A. Haman, P. Hugo, et al. Implication of Tyrosine Kinase Receptor and Steel Factor in Cell Density-dependent Growth in Cervical Cancers and Leukemias Cancer Res., August 1, 2001; 61(16): 6281 - 6289. [Abstract] [Full Text] [PDF]