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

Brahmchetna Singh, Richard F. Murphy, Xian Zhong Ding, Alexandra B. Roginsky, Richard H. Bell, Thomas E. Adrian

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

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.

Original languageEnglish
Article number82
JournalMolecular Cancer
Volume6
DOIs
Publication statusPublished - Dec 24 2007
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

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