Mutational analysis of the peroxisome proliferator-activated receptor γ in human malignancies

Peroxisome proliferator-activated receptor γ (PPARγ) 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 PPARγ 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 PPARγ gene is functionally mutated in sporadic colon cancer cells. Therefore, PPARγ could be an important tumor suppressor gene. This prompted us to investigate the expression and mutational status of the PPARγ gene in cancers of a variety of tissues. A total of 159 samples were interrogated for their expression of PPARγ as measured by reverse transcription-polymerase chain reaction and/or Western blot analysis. In each of the samples, expression of PPARγ 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 PPARγ 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, PPARγ is expressed in a variety of cancers, and mutation of the PPARγ gene is a very rare event in human malignancies.