Cancer Cell Biology and Oncogenomics - John A. Copland

TGFbeta Receptor and GATA3 Biology in Renal Cell Carcinoma

Immunohistochemistry of TGFbeta receptors in renal cell carcinoma shows loss of expression from the areas of metastasis.

Genomic profiling of normal kidney and clear cell renal cell carcinoma (ccRCC) patient tissues has identified that the expression of the type III TGFbeta receptor (TBR3) is lost as an early event in ccRCC.

Loss of TBR3 expression in renal cells leads to decreased responsiveness of cells to endogenous TGFbeta signaling, whose downstream pathways play roles in cell proliferation, differentiation, apoptosis, development, tissue repair, cell motility, extracellular matrix production, immunosuppression, migration and cancer.

Findings from the laboratory of John A. Copland, Ph.D., have identified that the loss of TBR3 expression in ccRCC is through epigenetic silencing of the transcription factor GATA3, a positive regulator of TBR3 expression in normal cells.

As a result, investigations are under way to identify mechanisms for the re-expression of these two genes in cancer cells and dissect downstream events that are influencing normal renal epithelial cell progression toward a cancer phenotype.