Sex-determining region Y box 4 is a transforming oncogene in human prostate cancer cells.
Prostate cancer is the most commonly diagnosed noncutaneous neoplasm and second most common cause of cancer-related mortality in western men. To investigate the mechanisms of prostate cancer development and progression, we did expression profiling of human prostate cancer and benign tissues. We show that the SOX4 is overexpressed in prostate tumor samples compared with benign tissues by microarray analysis, real-time PCR, and immunohistochemistry. We also show that SOX4 expression is highly correlated with Gleason score at the mRNA and protein level using tissue microarrays. Genes affected by SOX4 expression were also identified, including BCL10, CSF1, and NcoA4/ARA70. TLE-1 and BBC3/PUMA were identified as direct targets of SOX4. Silencing of SOX4 by small interfering RNA transfection induced apoptosis of prostate cancer cells, suggesting that SOX4 could be a therapeutic target for prostate cancer. Stable transfection of SOX4 into nontransformed prostate cells enabled colony formation in soft agar, suggesting that, in the proper cellular context, SOX4 can be a transforming oncogene.
Liu
Pengbo
P
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Ramachandran
Sumathi
S
Ali Seyed
Mohamed
M
Scharer
Christopher D
CD
Laycock
Noelani
N
Dalton
W Brian
WB
Williams
Holly
H
Karanam
Suresh
S
Datta
Milton W
MW
Jaye
David L
DL
Moreno
Carlos S
CS
D017209:Apoptosis / Q000235:genetics; D048708:Cell Growth Processes / Q000502:physiology; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D006609:High Mobility Group Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008297:Male; D009857:Oncogenes; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055751:SOXC Transcription Factors; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection
D006609:High Mobility Group Proteins; D034741:RNA, Small Interfering; C083431:SOX4 protein, human; D055751:SOXC Transcription Factors; D015534:Trans-Activators