The focus of the laboratory deals with the regulation and consequences of the coexpression of the c-kit receptor tyrosine kinase and its ligand, stem cell factor (SCF), in human tumors. The majority of small cell lung cancer and breast cancer cell lines coexpress the genes encoding c-kit and SCF. Studies in this laboratory, conducted by overexpressing c-kit in those cell lines that lack c-kit expression and by expression of dominant-negative mutants of c-kit in those cell lines that naturally express the gene, have demonstrated that activation of c-kit leads to enhanced growth factor independence. Ongoing studies are aimed at defining the signal transduction cascade leading from c-kit activation to alterations in tumor cell growth. In addition, we are also interested in the regulation of c-kit expression in these tumors. The c-kit promoter region has been cloned and a complete functional analysis is currently ongoing. We have observed that expression of c-kit positively correlates with the expression of N- and L-myc and negatively correlates with c-myc expression. The mechanism by which the myc family of transcription factors affects c-kit expression is being explored.
Krystal G, Armstrong B, Battey J: N-myc mRNA forms an RNA: RNA duplex with endogenous antisense transcripts. Mol. Cell. Biol., 10:4180-4191 (l990).
Levy J, Krystal G, Glickman P, Dastvan F: Insulin receptor gene expression in HepG2 cells: Effects of media conditions insulin and dexamethasone on insulin receptor mRNA on promoter activity in HepG2 cells. Diabetes, 40:58-65 (1991).
Krystal G: Regulation of eukaryotic gene expression by naturally occurring antisense RNA. In "Gene Regulation by Antisense RNA & DNA," Raven Press, New York, N.Y., pp. 11-20 (1992).
Armstrong B, Krystal G: Isolation and characterization of cDNA for N-cym, a gene encoded by the DNA strand opposite to N-myc. Cell Growth & Differentiation, 3:385-390 (1992).
Plummer III H, Catlett J, Leftwich J, Armstrong B, Carlson P, Huff T, and Krystal G. c-myc expression correlates with suppression of c-kit protooncogene expression in small cell lung cancer cell lines. Cancer Research 53: 4337-4342 (1993).
Ben-Ezra J, Grimes M, Kornstein M, Krystal G: Small cell carcinomas of the lung express the BCL-2 protooncogene. American Journal of Pathology, in press (1994).