1. Effect of transforming growth factor-beta1 on human intrahepatic cholangiocarcinoma cell growth
- Author
-
Koho Akimaru, Yoshiaki Mizuguchi, Takashi Tajiri, Yutaka Kawahigashi, Hiroshi Yoshida, Nobuhiko Taniai, Yasuo Arima, Tetsuya Shimizu, Yasuhiro Mamada, and Shigeki Yokomuro
- Subjects
STAT3 Transcription Factor ,Small interfering RNA ,Apoptosis ,Respiratory Mucosa ,Biology ,Protein Serine-Threonine Kinases ,Cell Line ,Cholangiocarcinoma ,Transforming Growth Factor beta1 ,Cell Line, Tumor ,Animals ,Humans ,RNA, Messenger ,Autocrine signalling ,Receptor ,Cell Proliferation ,Cell growth ,Interleukin-6 ,Gastroenterology ,Receptor, Transforming Growth Factor-beta Type II ,General Medicine ,Receptors, Interleukin-6 ,Cell biology ,Gene Expression Regulation, Neoplastic ,Bile Ducts, Intrahepatic ,Basic Research ,Bile Duct Neoplasms ,Cell culture ,Mink ,Cancer research ,RNA Interference ,Signal transduction ,Receptors, Transforming Growth Factor beta ,Transforming growth factor ,Signal Transduction - Abstract
To elucidate the biological effects of transforming growth factor-beta1 (TGF-beta1) on intrahepatic cholan-giocarcinoma (ICC).We investigated the effects of TGF-beta1 on human ICC cell lines (HuCCT1, MEC, and HuH-28) by monitoring the influence of TGF-beta1 on tumor growth and interleukin-6 (IL-6) expression in ICC cells.All three human ICC cell lines produced TGF-beta1 and demonstrated accelerated growth in the presence of TGF-beta1 with no apoptotic effect. Studies on HuCCT1 revealed a TGF-beta1-induced stimulation of the expression of TGF-beta1, as well as a decrease in TGF-beta1 mRNA expression induced by neutralizing anti-TGF-beta1 antibody. These results indicate that TGF-beta1 stimulates the production and function of TGF-beta1 in an autocrine fashion. Further, IL-6 secretion was observed in all three cell lines and exhibited an inhibitory response to neutralizing anti-TGF-beta1 antibody. Experiments using HuCCT1 revealed a TGF-beta1-induced acceleration of IL-6 protein expression and mRNA levels. These findings demonstrate a functional interaction between TGF-beta1 and IL-6. All three cell lines proliferated in the presence of IL-6. In contrast, TGF-beta1 induced no growth effect in HuCCT1 in the presence of small interfering RNA against a specific cell surface receptor of IL-6 and signal transducer and activator of transcription-3.ICC cells produce TGF-beta1 and confer a TGF-beta1-induced growth effect in an autocrine fashion. TGF-beta1 activates IL-6 production, and the functional interaction between TGF-beta1 and IL-6 contributes to ICC cell growth by TGF-beta1.
- Published
- 2006