Wen G Jiang

Publications (365) View all

• Article: Prognostic and therapeutic implications of mTORC1 and Rictor expression in human breast cancer.

  U Wazir, R F Newbold, W G Jiang, A K Sharma, K Mokbel
  [show abstract] [hide abstract]
  ABSTRACT: The mammalian target of rapamycin (mTOR) plays a key role in the regulation of cellular metabolism, growth and proliferation. It forms two multi-protein complexes known as complex 1 (mTORC1) and 2 (mTORC2). Raptor and Rictor are the core proteins for mTORC1 and mTORC2, respectively. This study examines the relationship between mTORC1, Rictor and Raptor mRNA expression and human breast cancer. Furthermore, the correlation between mTORC1 and hTERT was investigated. Breast cancer tissues (n=150) and normal tissues (n=31) were analysed using reverse transcription and quantitative PCR. Transcript levels were correlated with clinicopathological data. Higher mTOR expression was noted in breast cancer tissue (P=0.0018), higher grade tumours (grade 2 vs. 3, P=0.047), in ductal tumours (P=0.0014), and was associated with worse overall survival (P=0.01). Rictor expression was significantly higher in background breast tissues compared with tumours and was inversely related to the Nottingham Prognostic Index (NPI1 vs. 2, P=0.03) and tumour grade (grade 1 vs. 3, P=0.01) and was associated with better overall (P=0.037) and disease-free survival (P=0.048). The mRNA expression of Raptor was higher in tumours compared with normal tissues. Furthermore, the expression of Raptor was associated with a higher tumour grade (grade 1 vs. 3, P=0.027). A highly significant positive correlation between mTOR and hTERT (P<0.00001) was observed. These observations are consistent with the role of mTORC1 in the anti-apoptosis pathway and suggest that selective inhibitors of mTORC1 may be more efficacious in human breast cancer. Our findings support the hypothesis that mTORC1 is an important upregulator of telomerase in breast cancer.
  Oncology Reports 03/2013; · 1.84 Impact Factor
• Article: Comment on prognostic and therapeutic implications of mTORC2 and rictor expression in human breast cancer.

  U Wazir, R F Newbold, W G Jiang, A K Sharma, K Mokbel
  Breast Cancer Research and Treatment 09/2012; · 4.43 Impact Factor
• Article: CFTR suppresses tumor progression through miR-193b targeting urokinase plasminogen activator (uPA) in prostate cancer.

  C Xie, X H Jiang, J T Zhang, T T Sun, J D Dong, A J Sanders, R Y Diao, Y Wang, K L Fok, L L Tsang, [......], L Ye, M Y Zhao, J H Guo, Z J Xiao, H Y Lan, C F Ng, K M Lau, Z M Cai, W G Jiang, H C Chan
  [show abstract] [hide abstract]
  ABSTRACT: Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is expressed in the epithelial cells of a wide range of organs/tissues from which most cancers are derived. Although accumulating reports have indicated the association of cancer incidence with genetic variations in CFTR gene, the exact role of CFTR in cancer development and the possible underlying mechanism have not been elucidated. Here, we report that CFTR expression is significantly decreased in both prostate cancer cell lines and human prostate cancer tissue samples. Overexpression of CFTR in prostate cancer cell lines suppresses tumor progression (cell growth, adhesion and migration), whereas knockdown of CFTR leads to enhanced malignancies both in vitro and in vivo. In addition, we demonstrate that CFTR knockdown-enhanced cell proliferation, cell invasion and migration are significantly reversed by antibodies against either urokinase plasminogen activator (uPA) or uPA receptor (uPAR), which are known to be involved in various malignant traits of cancer development. More interestingly, overexpression of CFTR suppresses uPA by upregulating the recently described tumor suppressor microRNA-193b (miR-193b), and overexpression of pre-miR-193b significantly reverses CFTR knockdown-enhanced malignant phenotype and abrogates elevated uPA activity in prostate cancer cell line. Finally, we show that CFTR gene transfer results in significant tumor repression in prostate cancer xenografts in vivo. Taken together, the present study has demonstrated a previously undefined tumor-suppressing role of CFTR and its involvement in regulation of miR-193b in prostate cancer development.Oncogene advance online publication, 16 July 2012; doi:10.1038/onc.2012.251.
  Oncogene 07/2012; · 6.37 Impact Factor
• Article: The mRNA expression of DAP1 in human breast cancer: correlation with clinicopathological parameters.

  U Wazir, W G Jiang, A K Sharma, K Mokbel
  [show abstract] [hide abstract]
  ABSTRACT: This pilot study is the first to focus on the potential role of death-associated protein 1 (DAP1) in human breast cancer. A total of 153 samples were studied. DAP1 transcription levels were determined using quantitative polymerase chain reaction (qPCR). Transcript levels within breast cancer specimens were compared to those of normal background tissues and correlated with clinicopathological data accumulated over a 10-year follow-up period. The expression of DAP1 mRNA was demonstrated to decrease with increasing Nottingham Prognostic Index (NPI2 vs. NPI3, p=0.0026), and TNM stage (TNM1 vs. 4, p=0.0039). Lower DAP1 expression levels were significantly associated with local recurrence (p=0.02) and distant metastasis (p=0.001). This study demonstrates an inverse association between DAP1 mRNA levels and tumour stage and clinical outcome in breast cancer; thus, providing evidence that DAP1 plays a pro-apoptotic role in human breast cancer. The relationship between oncogenesis and the autophagy pathway merits further investigation.
  Cancer genomics & proteomics. 07/2012; 9(4):199-201.
• Article: The role of transglutaminases in the pathophysiology of prostate cancer.

  R J Ablin, W G Jiang
  Current Oncology 10/2011; 18(5):241-2. · 2.47 Impact Factor