Role of GLI2 transcription factor in growth and tumorigenicity of prostate cells.
Aberrant activation of the Hedgehog (Hh) signaling pathway has been reported in various cancer types including prostate cancer. The GLI2 transcription factor is a primary mediator of Hh signaling. However, its relative contribution to development of prostate tumors is poorly understood. To establish the role of GLI2 in maintaining the tumorigenic properties of prostate cancer cells, we developed GLI2-specific small hairpin RNA. Knockdown of GLI2 in these cells resulted in significant down-regulation of the Hh signaling pathway, followed by inhibition of colony formation, anchorage-independent growth, and growth of xenografts in vivo. Conversely, ectopic expression of Gli2 in nontumorigenic prostate epithelial cells resulted in accelerated cell cycle progression, especially transition through G(2)-M, and augmented proliferation. Altogether, our findings suggest that GLI2 plays a critical role in the malignant phenotype of prostate cancer cells, and GLI2 may potentially become an attractive therapeutic target for the treatment of prostate cancer.
Thiyagarajan
Saravanan
S
Department of Dermatology and Paul P. Carbone Comprehensive Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706, USA.
Bhatia
Neehar
N
Reagan-Shaw
Shannon
S
Cozma
Diana
D
Thomas-Tikhonenko
Andrei
A
Ahmad
Nihal
N
Spiegelman
Vladimir S
VS
D002453:Cell Cycle; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism / Q000502:physiology*; D008297:Male; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D010641:Phenotype; D011467:Prostate / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000473:pathology*; D015398:Signal Transduction; D000075746:Zinc Finger Protein Gli2
C082593:GLI2 protein, human; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D000075746:Zinc Finger Protein Gli2