PMID- 20127734
OWN - NLM
STAT- MEDLINE
DCOM- 20100513
LR  - 20211203
IS  - 1097-0045 (Electronic)
IS  - 0270-4137 (Linking)
VI  - 70
IP  - 8
DP  - 2010 Jun 1
TI  - Regulation of androgen receptor transactivity and mTOR-S6 kinase pathway by Rheb 
      in prostate cancer cell proliferation.
PG  - 866-74
LID - 10.1002/pros.21120 [doi]
AB  - BACKGROUND: Ras homolog-enriched in brain (Rheb), a small GTP-binding protein, is 
      associated with prostate carcinogenesis through activating mammalian target of 
      rapamycin (mTOR) signaling pathway. This study aimed to elucidate whether Rheb 
      promotes proliferation of prostate cancer cells and can act as a potent 
      therapeutic target in prostate cancer. METHODS: Prostate cancer cell lines and 
      human prostatic tissues were examined for the expression of Rheb. The effects of 
      forced expression or knockdown of Rheb on cell proliferation were also examined. 
      Semi-quantitative and quantitative RT-PCR were performed to evaluate mRNA 
      expression. Western blotting was used to examine protein expression. Cell count 
      and WST-1 assay were used to measure cell proliferation. Fluorescence-activated 
      cell sorting was used to assess the cell cycle. RESULTS: Rheb mRNA and protein 
      expression was higher in more aggressive, androgen-independent prostate cancer 
      cell lines PC3, DU145, and C4-2, compared with the less aggressive LNCaP. Rheb 
      expression was higher in cancer tissues than in benign prostatic epithelia. 
      Forced expression of Rheb in LNCaP cells accelerated proliferation without 
      enhancing androgen receptor transactivity. Attenuation of Rheb expression or 
      treatment with the mTOR inhibitor rapamycin decreased proliferation of PC3 and 
      DU145 cells, with a decrease in the activated form of p70S6 kinase, one of the 
      main targets of mTOR. CONCLUSIONS: Rheb potentiates proliferation of prostate 
      cancer cells and inhibition of Rheb or mTOR can lead to suppressed proliferation 
      of aggressive prostate cancer cell lines in vitro. Rheb and the mTOR pathway are 
      therefore probable targets for suppressing prostate cancer.
FAU - Kobayashi, Takashi
AU  - Kobayashi T
AD  - Department of Urology, Kyoto University Graduate School of Medicine, Sakyo-ku, 
      Kyoto, Japan.
FAU - Shimizu, Yosuke
AU  - Shimizu Y
FAU - Terada, Naoki
AU  - Terada N
FAU - Yamasaki, Toshinari
AU  - Yamasaki T
FAU - Nakamura, Eijiro
AU  - Nakamura E
FAU - Toda, Yoshinobu
AU  - Toda Y
FAU - Nishiyama, Hiroyuki
AU  - Nishiyama H
FAU - Kamoto, Toshiyuki
AU  - Kamoto T
FAU - Ogawa, Osamu
AU  - Ogawa O
FAU - Inoue, Takahiro
AU  - Inoue T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Prostate
JT  - The Prostate
JID - 8101368
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Neuropeptides)
RN  - 0 (RHEB protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (Ras Homolog Enriched in Brain Protein)
RN  - 0 (Receptors, Androgen)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.6.5.2 (Monomeric GTP-Binding Proteins)
SB  - IM
MH  - Blotting, Western
MH  - Cell Count
MH  - Cell Cycle/*physiology
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Flow Cytometry
MH  - Humans
MH  - Immunohistochemistry
MH  - Intracellular Signaling Peptides and Proteins/genetics/*metabolism
MH  - Male
MH  - Monomeric GTP-Binding Proteins/genetics/*metabolism
MH  - Neuropeptides/genetics/*metabolism
MH  - Prostate/*metabolism
MH  - Prostatic Hyperplasia/genetics/metabolism
MH  - Prostatic Neoplasms/genetics/*metabolism
MH  - Protein Serine-Threonine Kinases/genetics/*metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Ras Homolog Enriched in Brain Protein
MH  - Receptors, Androgen/genetics/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/*physiology
MH  - TOR Serine-Threonine Kinases
EDAT- 2010/02/04 06:00
MHDA- 2010/05/14 06:00
CRDT- 2010/02/04 06:00
PHST- 2010/02/04 06:00 [entrez]
PHST- 2010/02/04 06:00 [pubmed]
PHST- 2010/05/14 06:00 [medline]
AID - 10.1002/pros.21120 [doi]
PST - ppublish
SO  - Prostate. 2010 Jun 1;70(8):866-74. doi: 10.1002/pros.21120.