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Mutational Analysis of the Peroxisome Proliferator-activated Receptor Gene in Human Malignancies¹

Division of Hematology/Oncology [T. I., C. W. M., S. K., E. A. W., J. H., E. G., W. H., H. P. K.] and Department of Medicine [A. H.], Cedars-Sinai Research Institute, University of California-Los Angeles School of Medicine, Los Angeles, California 90048, and Department of Medicine, Kochi Medical School, Kochi 783-8505, Japan [H. T.]

Peroxisome proliferator-activated receptor (PPAR) plays an important role in adipocyte differentiation and is expressed in many human malignancies, including those from prostate, breast, as well as colon. It regulates differentiation and/or cell growth of these cells. However, expression of this nuclear hormone receptor in other types of cancer, especially in hematological malignancies, remains to be fully elucidated. The PPAR gene has been mapped to chromosome band 3p25, where chromosomal abnormalities are observed in a variety of human malignancies. Furthermore, a recent study revealed that the PPAR gene is functionally mutated in sporadic colon cancer cells. Therefore, PPAR could be an important tumor suppressor gene. This prompted us to investigate the expression and mutational status of the PPAR gene in cancers of a variety of tissues. A total of 159 samples were interrogated for their expression of PPAR as measured by reverse transcription-polymerase chain reaction and/or Western blot analysis. In each of the samples, expression of PPAR was detectable. In addition, a total of 397 clinical samples and cell lines including colon, prostate, breast and lung cancers, and leukemias were analyzed for mutations of the PPAR gene by either reverse transcription-polymerase chain reaction-single-strand conformation polymorphism or polymerase chain reaction-single-strand conformation polymorphism analysis. No abnormalities were detectable in any of the human malignancies. On the other hand, shifted bands were easily detectable when using positive controls, which harbored the same sequence alterations reported previously in colon cancer cells. Taken together, PPAR is expressed in a variety of cancers, and mutation of the PPAR gene is a very rare event in human malignancies.

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