Cultured human pancreatic cancer cells produce transforming growth factor-α (TGF-α), a potent mitogenic polypeptide. In the present study, we investigated the regulation of TGF-α mRNA expression in T3M4human pancreatic carcinoma cells. TGF-α mRNA levels were quantitated by densi-tometric analysis of autoradiographs obtained following hybridization of size-fractionated cytoplasmic RNA with32P-labeled cRNA coding for human TGF-α. There was a twofold increase in TGF-α mRNA levels at 2 h following addition of either epidermal growth factor (EGF) or TGF-α. However, TGF-α mRNA levels declined to near basal levels by 10 h. At 2 h, one-half maximal stimulation of TGF-α mRNA levels occurred at 1 nM and maximal stimulation at 4 nM of either EGF or TGF-α. The transcriptional inhibitor actinomycin D (Act D) and the phorbol ester, 12-0-tetradecanoyl-phorbol-13-αcetate (TPA), mimicked the actions of EGF and TGF-α. These findings indicate that the regulation of TGF-α mRNA expression in T3M4cells is complex, and is me-diated, in part, via the EGF receptor.
- Autocrine regulation
- Epidermal growth factor receptor
- Pancreatic cancer
- Transforming growth factor-α
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism