Livin-α promotes cell proliferation by regulating G1-S cell cycle transition in prostate cancer.
BACKGROUND
Prostate cancer is the third most common cancer and the second leading cause of cancer death for males in US. Livin has recently been described as a cancer-associated member of inhibitor of apoptosis proteins family, highly expressed in prostate cancer. Livin gene encodes two splicing variants, termed Livin-α and Livin-β. We hypothesized that deregulation of proliferation could be due in part to Livin expression.


METHODS
Pathological analysis of Livin was performed in 20 prostate cancer tissues and 5 benign prostatic hyperplasia tissues. The expression of Livin isoforms was also investigated by Western blot in prostate cancer cell lines LNCaP and PC3. The role of Livin-α in vitro was further studied. Using Livin-α knockdown and overexpression models, cell cycle analysis, Ki-67 immunocytostaining, and MTT assay were performed respectively.


RESULTS
Livin expression positive ratio was shown to be 5.4%, 23.6%, 52.4%, 73.4% in benign prostatic hyperplasia, low, medium, and high grade of prostate cancer respectively, and Livin was positively correlated with clinical pathological grades of prostate cancer. Livin-α was expressed in both LNCaP and PC3; meanwhile; Livin-β was only detected in the PC3. Livin-α siRNA not only resulted in G(1)-S cell cycle arrest, but also strongly correlated with the descended proliferation index and survival rate in LNCaP. In comparison, overexpression of Livin-α resulted in an accelerated S phase entry combined with elevated proliferation index and survival in LNCaP.


CONCLUSIONS
Livin-α may promote cell proliferation by regulating G(1)-S cell cycle transition and possibly play an important part in initiation of prostate cancer.
Ye
Lin
L
Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
Song
Xishuang
X
Li
Sheng
S
Yang
Deyong
D
Zhang
Jianing
J
Che
Xiangyu
X
Chen
Xiaochi
X
Wang
Jianbo
J
Zhang
Zhiwei
Z
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000230:Adenocarcinoma / Q000473:pathology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000502:physiology*; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D009363:Neoplasm Proteins / Q000502:physiology*; D011470:Prostatic Hyperplasia / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D020033:Protein Isoforms / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; C419866:BIRC7 protein, human; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D020033:Protein Isoforms