Activation of PPARγ leads to inhibition of anchorage-independent growth of human colorectal cancer cells

J. A. Brockman, R. A. Gupta, R. N. Dubois

Research output: Contribution to journalArticle

292 Citations (Scopus)

Abstract

Background and Aims: Peroxisomal proliferator-activated receptor γ (PPARγ) is a nuclear hormone receptor that provides a direct link between fatty acid metabolism and control of gene transcription. The objective of this study was to determine the biological effect(s) of PPARγ, activation in colorectal carcinoma cells. Methods: PPARγ expression and activity were measured in 4 human colon cancer cell lines using reverse-transcription polymerase chain reaction, immunoprecipitation and immunoblotting, and transient reporter gene assays. The effects of activated PPARγ in these cell lines were assessed in cellular proliferation and anchorage-independent growth assays. Flow cytometry was used to determine the effects of PPARγ activation on progression through the cell cycle. Results: PPARγ was expressed in all 4 colon cancer cell lines examined and was transcriptionally functional in 3 of the 4. Treatment of these cells with a selective PPARγ activator (BRL 49653) resulted in inhibition of anchorage-independent growth. The degree of growth inhibition correlated with the level of functional PPARγ present. Finally, activation of PPARγ resulted in G1 cell cycle arrest. Conclusions: Activation of the PPARγ pathway in colon cancer cells has potent antiproliferative effects, suggesting that this nuclear hormone receptor may provide a novel target for prevention and treatment of colorectal cancer in humans.

Original languageEnglish (US)
Pages (from-to)1049-1055
Number of pages7
JournalGastroenterology
Volume115
Issue number5
DOIs
StatePublished - 1998
Externally publishedYes

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Colonic Neoplasms
Colorectal Neoplasms
rosiglitazone
Cytoplasmic and Nuclear Receptors
Cell Line
Growth
G1 Phase Cell Cycle Checkpoints
Reporter Genes
Immunoprecipitation
Immunoblotting
Reverse Transcription
Cell Cycle
Flow Cytometry
Fatty Acids
Cell Proliferation
Polymerase Chain Reaction
Genes

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Activation of PPARγ leads to inhibition of anchorage-independent growth of human colorectal cancer cells. / Brockman, J. A.; Gupta, R. A.; Dubois, R. N.

In: Gastroenterology, Vol. 115, No. 5, 1998, p. 1049-1055.

Research output: Contribution to journalArticle

Brockman, J. A. ; Gupta, R. A. ; Dubois, R. N. / Activation of PPARγ leads to inhibition of anchorage-independent growth of human colorectal cancer cells. In: Gastroenterology. 1998 ; Vol. 115, No. 5. pp. 1049-1055.
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