Somatic mutations in peroxisome proliferator-activated receptor-gamma are rare events in human cancer cells.

Abstract

BACKGROUND:

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a nuclear hormone receptor activated after binding a lipophilic ligand, such as naturally occurring 15dPGJ2. There is striking evidence that PPAR-gamma activation leads not only to an increase in insulin sensitivity, but also to tumor cell apoptosis and cell cycle arrest. A growing number of diabetes mellitus II patients currently benefit from treatment with synthetic PPAR-gamma agonists, the thiazolidinediones (TZDs), which sensitize peripheral cells towards insulin. Furthermore, some TZDs are undergoing clinical investigations for the treatment of malignant diseases. Therefore, detailed information on the frequency of genetic alterations of PPAR-gamma in malignant tumor cells is necessary.

MATERIAL/METHODS:

PPAR-gamma DNA of 33 histologically different tumor cells was isolated, purified, and all coding regions were separately amplified by PCR. The coding exons were then analyzed by single-stranded conformational polymorphism (SSCP) and bidirectional DNA sequencing.

RESULTS:

In five breast cancer brain metastasis samples from patients and 28 cancer cell lines derived from lymphoma, glioblastoma, and breast carcinoma we found only one coding region shift in exon 5b of the glioblastoma U373 DNA. This silent mutation does not lead to a change in amino acid alignment. No further polymorphisms, including those which have already been described, could be detected in any other sample.

CONCLUSIONS:

We conclude that somatic mutations in the PPAR gene are exceedingly rare events in malignant tumor cells. This makes PPAR-gamma more unlikely to act as a tumor suppressor gene, making it a stable and suitable target for TZD biological cancer therapy.

• Authors: Maximilian G Posch, Chuanbing Zang, Wolf Mueller, Ulrike Lass, Andreas von Deimling, Elena Elstner
• Journal: Medical science monitor : international medical journal of experimental and clinical research (Med Sci Monit) Vol. 10 Issue 8 Pg. BR250-4 (Aug 2004) ISSN: 1234-1010 [Print] United States
• PMID: 15277984 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Primers

Topics

• Brain Neoplasms (genetics, secondary)
• Breast Neoplasms (genetics, pathology)
• DNA Primers
• Female
• Humans
• Neoplasms (genetics)
• Polymorphism, Single-Stranded Conformational
• Tumor Cells, Cultured