Charles Roberts

Growth Factor-Tumor Suppressor Interactions

The insulin-like growth factors (IGFs) are important regulators of normal growth and development, and are implicated in the development and progression of breast and prostate cancer. The actions of these factors are mediated through their activation of the IGF-I receptor, a transmembrane tyrosine kinase that is coupled to the MAPK, P13K and STAT signaling pathways. IGF-I receptor function has been demonstrated to be necessary for the tumorigenicity of numerous cell types and for the transformation of fibroblasts by a wide variety of oncogenes. Cellular responsiveness to IGFs is a function of cell-surface IGF-I receptor number, which is principally determined by IGF-I receptor gene expression. Our research is focused on the molecular mechanisms involved in the transcriptional regulation of the IGF-I receptor gene, in particular the roles of the WT1 and p53 tumor suppressors and their functional relationship to the action of general transcription factors such as Sp1. The elucidation of the interactions that govern the activity of the IGF-I receptor gene will provide insights into the development of the transformed phenotype and may identify therapeutic targets for cancer therapy.

Silberbach, M., Gorenc, T., Hershberger, R.E., Stork, P.J.S., Steyger, P.S., and Roberts, C.T., Jr. (1999). ERK activation is required for the anti-hypertrophic effect of atrial natriuretic factor in neonatal rat ventricular myocytes. J. Biol. Chem. 274, 24858-24864.

Tajinda, K., Carroll, J., and Roberts, C.T., Jr. (1999). Regulation of IGF-I receptor activity by wild-type and mutant versions of the WT1 tumor suppressor. Endocrinology 140, 4713-4724.

Damon, S.E., Plymate, S.R., Carroll, J.M., Sprenger, C.C., Dechsukhum, C., Ware, J.L., and Roberts, C.T. Jr. (2000). Transcriptional regulation of IGF-I receptor gene expression in prostate cancer cells. Endocrinology (in press).

To contact Dr. Roberts directly: robertsc@ohsu.edu