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

Peroxisome proliferator-activated receptor gamma (PPAR gamma) plays an impo rtant role in adipocyte differentiation and is expressed in many human mali gnancies, including those from prostate, breast, as well as colon. It regul ates differentiation and/or cell growth of these cells. However, expression of this nuclear hormone receptor in other types of cancer, especially in h ematological malignancies, remains to be fully elucidated. The PPAR gamma g ene has been mapped to chromosome band 3p25, where chromosomal abnormalitie s are observed in a variety of human malignancies. Furthermore, a recent st udy revealed that the PPAR gamma gene is functionally mutated in sporadic c olon cancer cells. Therefore, PPAR gamma could be an important tumor suppre ssor gene. This prompted us to investigate the expression and mutational st atus of the PPAR gamma gene in cancers of a variety of tissues. A total of 159 samples were interrogated for their expression of PPAR gamma as measure d by reverse transcription-polymerase chain reaction and/or Western blot an alysis. In each of the samples, expression of PPAR gamma 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 mutation s of the PPAR gamma gene by either reverse transcription-polymerase chain r eaction-single-strand conformation polymorphism or polymerase chain reactio n-single-strand conformation polymorphism analysis. No abnormalities were d etectable in any of the human malignancies. On the other hand, shifted band s were easily detectable when using positive controls, which harbored the s ame sequence alterations reported previously in colon cancer cells. Taken t ogether, PPAR gamma is expressed in a variety of cancers, and mutation of t he PPAR gamma gene is a very rare event in human malignancies.