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

Abstract

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. 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. 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. 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.