Activation of the mammalian target of rapamycin signalling pathway in prostate cancer and its association with patient clinicopathological characteristics.
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.


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.
Dai
Bo
B
Department of Urology, Cancer Hospital, Fudan University, Shanghai, China.
Kong
Yun Yi
YY
Ye
Ding Wei
DW
Ma
Chun Guang
CG
Zhou
XiaoYan
X
Yao
Xu Dong
XD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011470:Prostatic Hyperplasia / Q000378:metabolism; D019048:Prostatic Intraepithelial Neoplasia / Q000378:metabolism* / Q000628:therapy; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000628:therapy; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases
D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus