Up-regulation of tumor susceptibility gene 101 conveys poor prognosis through suppression of p21 expression in ovarian cancer.
OBJECTIVE
The function of tumor susceptibility gene 101 (TSG101) in ovarian carcinogenesis is largely unexplored. The aim of this study is to investigate the role of TSG101 in human ovarian cancer development, to examine the expression levels of TSG101 in ovarian carcinomas, and to correlate the results with clinicopathologic variables and survival.


METHODS
Human ovarian cancer tissue arrays that contain duplicates of 422 cases of primary ovarian carcinoma were used to probe the expression levels of TSG101 and p21 in epithelial ovarian cancer. In vitro studies in ovarian cancer cells using TSG101-specific small interfering RNA (siRNA) were done to further elucidate the mechanism of TSG101-mediated p21 regulation.


RESULTS
We show that TSG101 is increasingly overexpressed in borderline tumors and low-grade and high-grade carcinomas. Patients with low expression of TSG101 survive longer than those with high expression. Suppressing TSG101 by siRNA in ovarian cancer cells led to growth inhibition, cell cycle arrest, and apoptosis with concurrent increases in p21 mRNA and protein. Consistent with this negative association between TSG101 and p21, expression levels of these two markers are inversely correlated in ovarian cancer.


CONCLUSIONS
TSG101 negatively regulates p21 levels, and up-regulation of TSG101 is associated with poor prognosis in ovarian cancer.
Young
Travis W
TW
Department of Pharmacology and Toxicology, Sealy Center for Cancer Cell Biology, The University of Texas Medical Branch, Galveston, Texas 77555-1031, USA.
Rosen
Daniel G
DG
Mei
Fang C
FC
Li
Nan
N
Liu
Jinsong
J
Wang
Xiao-Fan
XF
Cheng
Xiaodong
X
D000368:Aged; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D018450:Disease Progression; D056827:Endosomal Sorting Complexes Required for Transport; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000378:metabolism*; D011379:Prognosis; D034741:RNA, Small Interfering / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000096:biosynthesis*; D014162:Transfection; D015854:Up-Regulation; D000099177:Tsg101 Protein
D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D034741:RNA, Small Interfering; D014157:Transcription Factors; D000099177:Tsg101 Protein; C493956:CDKN1A protein, human