PMID- 19389013
OWN - NLM
STAT- MEDLINE
DCOM- 20101014
LR  - 20211203
IS  - 1464-410X (Electronic)
IS  - 1464-4096 (Linking)
VI  - 104
IP  - 7
DP  - 2009 Oct
TI  - Activation of the mammalian target of rapamycin signalling pathway in prostate 
      cancer and its association with patient clinicopathological characteristics.
PG  - 1009-16
LID - 10.1111/j.1464-410X.2009.08538.x [doi]
AB  - OBJECTIVE: To evaluate the activation level of the mammalian target of rapamycin 
      (mTOR) signalling pathway in Chinese patients with prostate cancer, as this 
      pathway is over-activated in many human cancers and is an attractive target for 
      cancer therapy. PATIENTS AND METHODS: We used immunohistochemistry to investigate 
      the activation level of five important markers of the mTOR pathway, including 
      PTEN, p-Akt, p-mTOR, p-p70S6K and p-4E-BP1, in tissues from 182 patients with 
      prostate cancer, 20 with benign prostatic hyperplasia (BPH) and 10 with 
      high-grade prostatic intraepithelial neoplasia (HGPIN). The expression levels of 
      these five markers were associated with patient clinical and pathological 
      characteristics. RESULTS: Expression levels of p-Akt, p-mTOR, p-4E-BP1 and 
      p-p70S6K were significantly higher in prostate cancer tissues than in BPH and 
      HGPIN tissues. In 182 patients with prostate cancer the p-mTOR expression level 
      significantly and positively correlated with its upstream p-Akt and downstream 
      p-4E-BP1 and p-p70S6K expression levels. The cancer Gleason score was 
      significantly correlated with p-Akt and p-mTOR expression level but not with 
      p-4E-BP1 and p-p70S6K expression level. However, the p-4E-BP1 and p-p70S6K 
      expression levels in primary cancer lesions were statistically significantly 
      correlated with patient T stage and distant metastases. CONCLUSIONS: Most 
      patients with prostate cancer have at least one component of the mTOR signalling 
      pathway activated. The activation of the mTOR pathway might be involved in 
      prostate cancer development and progression. The association between activation 
      of mTOR pathway and patient clinicopathological variables suggested that not all 
      patients are equally amenable to treatment strategies targeting the mTOR pathway.
FAU - Dai, Bo
AU  - Dai B
AD  - Department of Urology, Cancer Hospital, Fudan University, Shanghai, China.
FAU - Kong, Yun Yi
AU  - Kong YY
FAU - Ye, Ding Wei
AU  - Ye DW
FAU - Ma, Chun Guang
AU  - Ma CG
FAU - Zhou, XiaoYan
AU  - Zhou X
FAU - Yao, Xu Dong
AU  - Yao XD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090415
PL  - England
TA  - BJU Int
JT  - BJU international
JID - 100886721
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
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  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/*metabolism
MH  - Disease Progression
MH  - Humans
MH  - Immunohistochemistry
MH  - Intracellular Signaling Peptides and Proteins/antagonists & 
      inhibitors/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Phosphorylation
MH  - Prostatic Hyperplasia/metabolism
MH  - Prostatic Intraepithelial Neoplasia/*metabolism/therapy
MH  - Prostatic Neoplasms/*metabolism/therapy
MH  - Protein Serine-Threonine Kinases/antagonists & inhibitors/*metabolism
MH  - Signal Transduction/*physiology
MH  - Sirolimus
MH  - TOR Serine-Threonine Kinases
EDAT- 2009/04/25 09:00
MHDA- 2010/10/15 06:00
CRDT- 2009/04/25 09:00
PHST- 2009/04/25 09:00 [entrez]
PHST- 2009/04/25 09:00 [pubmed]
PHST- 2010/10/15 06:00 [medline]
AID - BJU8538 [pii]
AID - 10.1111/j.1464-410X.2009.08538.x [doi]
PST - ppublish
SO  - BJU Int. 2009 Oct;104(7):1009-16. doi: 10.1111/j.1464-410X.2009.08538.x. Epub 
      2009 Apr 15.