Abstract
Several colonic and gastric cancer cell lines express peroxisome proliferator activated receptor γ (PPARγ), a member of the nuclear receptor superfamily. The thiazolidinedione class of antidiabetic drugs including troglitazone and rosiglitazone are known to be ligands for PPARγ. Treatment with troglitazone inhibits the growth of colonic cancer cells and promotes their differentiation. Troglitazone also inhibits the growth of MKN-45 gastric cancer cells, which overexpress c-Met tyrosine kinase. Thus PPARγ ligands may be candidates for a novel approach to the treatment of gastric and colorectal cancers. Ligand activation of PPARγ reduces the expression of c-Met tyrosine kinase, which is suggested to be one mechanism by which troglitazone inhibits the growth of MKN-45 cells. The mechanisms whereby PPARγ inhibits the growth of gastric and colorectal carcinoma cells in general remain unknown. Further investigations are needed to clarify the role of PPARγ in the proliferation and differentiation of gastrointestinal epithelial cells.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Chawla A, Schwarz EJ, Dimaculangan DD, et al (1994) Peroxisome proliferator-activated receptor (PPAR) γ. adipose-predominant expression and induction early in adipocyte differentiation. Endocrinology 135:798–800
Kitamura S, Miyazaki Y, Shinomura Y, et al (1999) Peroxisome proliferator-activated receptor γ induces growth arrest and differentiation markers of human colon cancer cells. Jpn J Cancer Res 90:75–80
Lefebvre AM, Chen I, Desreumaux P, et al (1998) Activation of the peroxisome proliferator-activated receptor γ promotes the development of colon tumors in C57BL/6J-APCMin/+mice. Nat Med 4:1053–1057
Saez E, Tontonoz P, Nelson MC, et al (1998) Activators of the nuclear receptor PPARγ enhance colon polyp formation. Nat Med 4:1058–1061
Kitamura S, Miyazaki Y, Hiraoka S, et al (1999) PPARγ inhibits the expression of c-MET in human gastric cancer cells through the suppression of Ets. Biochem Biophys Res Commun 265:453–456
Altiok S, Xu M, Spiegelman BM (1997) PPARγ induces cell cycle withdrawal: inhibition of E2F/DP DNA-binding activity via down-regulation of PP2A. Genes Dev 11: 1987–1998
Ricote M, Li AC, Willson TM, et al (1998) The peroxisome proliferator-activated receptor-γ is a negative regulator of macrophage activation. Nature 391:79–82
Jiang C, Ting AT, Seed B (1998) PPAR-γ agonists inhibit production of monocyte inflammatory cytokines. Nature 391:82–86
Yang XY, Wang LH, Chen T, et al (2000) Activation of human T lymphocytes is inhibited by peroxisome proliferator-activated receptor γ (PPARγ) agonists: PPARγ co-association with transcription factor NFAT. J Biol Chem 275:4541–4544
Gelman L, Fruchart JC, Auwerx J (1999) An update on the mechanisms of action of the peroxisome proliferator-activated receptors (PPARs) and their roles in inflammation and cancer. Cell Mol Life Sci 55:932–943
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2001 Springer Japan
About this paper
Cite this paper
Miyazaki, Y., Kitamura, S., Shinomura, Y., Matsuzawa, Y. (2001). Role of PPARγ in the Growth and Differentiation of Gastric and Colorectal Cancers. In: Asakura, H., Aoyagi, Y., Nakazawa, S. (eds) Trends in Gastroenterology and Hepatology. Springer, Tokyo. https://doi.org/10.1007/978-4-431-67895-3_23
Download citation
DOI: https://doi.org/10.1007/978-4-431-67895-3_23
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-67993-6
Online ISBN: 978-4-431-67895-3
eBook Packages: Springer Book Archive