Research

On the role of transforming growth factor-β in the growth inhibitory effects of retinoic acid in human pancreatic cancer cells

Brahmchetna Singh^1,2 , Richard F Murphy² , Xian-Zhong Ding¹ , Alexandra B Roginsky¹ , Richard H Bell Jr¹ and Thomas E Adrian^1,3

¹  Department of Surgery and Robert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

²  Department of Biomedical Sciences, Creighton University, Omaha, NE, USA

³  Department of Physiology, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE

author email corresponding author email

Molecular Cancer 2007, 6:82doi:10.1186/1476-4598-6-82

Published:	24 December 2007

Abstract

Background

Retinoids are potent growth inhibitory and differentiating agents in a variety of cancer cell types. We have shown that retinoids induce growth arrest in all pancreatic cancer cell lines studied, regardless of their p53 and differentiation status. However, the mechanism of growth inhibition is not known. Since TGF-β2 is markedly induced by retinoids in other cancers and mediates MUC4 expression in pancreatic cancer cells, we investigated the role of TGF-β in retinoic acid-mediated growth inhibition in pancreatic cancer cells.

Results

Retinoic acid markedly inhibited proliferation of two cell lines (Capan-2 and Hs766T) in a concentration and time-dependent manner. Retinoic acid increased TGF-β2 mRNA content and secretion of the active and latent forms of TGF-β2 (measured by ELISA and bioassay). The concentrations of active and TGF-β2 secreted in response to 0.1 – 10 μM retinoic acid were between 1–5 pM. TGF-β2 concentrations within this range also inhibited proliferation. A TGF-β neutralizing antibody blocked the growth inhibitory effects of retinoic acid in Capan-2 cells and partially inhibitory the effects in Hs766T cells.

Conclusion

These findings indicate that TGF-β can cause growth inhibition of pancreatic cancer cells, in a p53-independent manner. Furthermore, it demonstrates the fundamental role of TGF-β in growth inhibition in response to retinoic acid treatment is preserved in vitro.