TGFBR3 loss and consequences in prostate cancer.
BACKGROUND
Resistance to transforming growth factor-beta (TGF-beta) is important in tumorigenesis. TGF-beta resistance mechanisms in prostate cancer are not well understood.


METHODS
We have conducted a systematic analysis of TGF-beta pathway components with a meta-analysis of seven microarray studies using Oncomine and evaluated the results of TGFBR3 expression in prostate cell lines. Furthermore, we knocked down TGFBR3 in prostate epithelial cells and analyzed the consequences of TGFBR3 knockdown.


RESULTS
We found that TGFBR3 is the TGF-beta component most commonly downregulated among localized human prostate cancer studies. TGFBR3 knockdown led to focus formation and enhanced expression of CD133, a marker found on prostate cancer stem cells. DNA microarray analysis of TGFBR3 knockdown cells identified 101 genes regulated by TGFBR3. Seven of these genes show a corresponding decrease in clinical prostate cancer specimens, which include genes involved in prostate mass and vasculature.


CONCLUSIONS
TGFBR3 downregulation is an important step in prostate tumorigenesis.
Sharifi
Nima
N
Cancer Stem Cell Section, Laboratory of Cancer Prevention, National Cancer Institute at Frederick, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702, USA. nima.sharifi@nih.gov
Hurt
Elaine M
EM
Kawasaki
Brian T
BT
Farrar
William L
WL
D015153:Blotting, Western; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D011509:Proteoglycans / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D011509:Proteoglycans; D012334:RNA, Neoplasm; D018125:Receptors, Transforming Growth Factor beta; C071736:betaglycan