Production of transforming growth factor alpha in human pancreatic cancer cells: evidence for a superagonist autocrine cycle.

Publisher Website
Google Scholar
Abstract
Previous work showed that cultured human pancreatic cancer cells overexpress the epidermal growth factor (EGF) receptor. In the present study, we sought to determine whether some of these cell lines produce transforming growth factor .alpha.(TGF-.alpha.). Utilizing a radiolabeled TGF-.alpha. cDNA in hybridization experiments, we determined that ASPC-1, T3M4, PANC-1, COLO-357, and MIA PaCa-2 cell lines expressed TGF-.alpha. mRNA. Serum-free medium conditioned by T3M4 and ASPC-1 cells contained significant amounts of TGF-.alpha. protein. Although unlabeled TGF-.alpha. readily competed with 125I-labeled EGF for binding, each cell line exhibited lower surface binding and internalization of 125I-labeled TGF-.alpha. as compared to 125I-labeled EGF. Both TGF-.alpha. and EGF significantly enhanced the anchorage-independent growth of PANC-1, T3M4, and ASPC-1 cells. However, TGF-.alpha. was 10- to 100-fold more potent than EGF. These findings suggest that the concomitant overexpression of EGF receptors and production of TGF-.alpha. may represent an efficient mechanism for certain cancer cells to obtain a growth advantage.