Patient samples of renal cell carcinoma show reduced expression of TRAF1 compared with normal kidney and functional studies in vitro indicate TRAF1 promotes apoptosis: Potential for targeted therapy

Rajandram, Retnagowri, Bennett, Nigel C., Wang, Zhiqiang, Perry-Keene, Joanna, Vesey, David A., Johnson, David W. and Gobe, Glenda C. (2012) Patient samples of renal cell carcinoma show reduced expression of TRAF1 compared with normal kidney and functional studies in vitro indicate TRAF1 promotes apoptosis: Potential for targeted therapy. Pathology, 44 5: 453-459. doi:10.1097/PAT.0b013e3283557748


Author Rajandram, Retnagowri
Bennett, Nigel C.
Wang, Zhiqiang
Perry-Keene, Joanna
Vesey, David A.
Johnson, David W.
Gobe, Glenda C.
Title Patient samples of renal cell carcinoma show reduced expression of TRAF1 compared with normal kidney and functional studies in vitro indicate TRAF1 promotes apoptosis: Potential for targeted therapy
Journal name Pathology   Check publisher's open access policy
ISSN 0031-3025
1465-3931
Publication date 2012-08
Sub-type Article (original research)
DOI 10.1097/PAT.0b013e3283557748
Volume 44
Issue 5
Start page 453
End page 459
Total pages 7
Place of publication London, United Kingdom
Publisher Lippincott Williams & Wilkins
Collection year 2013
Language eng
Formatted abstract
AB Aims: The tumour necrosis factor (TNF) receptor-associated factor (TRAF) family of proteins links the TNF receptor superfamily to cell signalling cascades. TRAF1 is involved in regulation of apoptosis, proliferation, differentiation and stress responses. It has a role in development of several malignancies, but no information for renal cell carcinoma (RCC) is available.

Methods: Expression profiles for TRAF1 were investigated in 121 samples of human RCC of various subtypes plus paired normal kidney prepared in tissue microarrays, in comparison with apoptosis (morphology, ApopTag) and mitosis (morphology, proliferating cell nuclear antigen/PCNA). TRAF1 function was tested in vitro in RCC ACHN cells. TRAF1 short interfering RNA (siRNA) was used to inhibit expression of TRAF1 in ACHN cells untreated or treated with cancer therapies known to induce apoptosis (20 Gy X-irradiation and/or 500 IU/mL interferon-alpha).

Results: In patient samples, TRAF1 localised to proximal tubular epithelium in normal kidney and was significantly decreased in clear cell RCC as one group (p < 0.01) and all other RCC subclassifications grouped together (p < 0.05). There was little apoptosis identified in any RCC samples. In vitro, TRAF1 siRNA caused significant reduction in TRAF1 expression and a concurrent decrease in apoptosis and increase in proliferative activity (both p < 0.05) in the ACHN RCC cells treated with radiation and interferon-alpha.

Conclusion: TRAF1 may have a pro-apoptotic, anti-mitotic role in RCC. The low TRAF1 expression in untreated RCC patient samples compared with normal kidney, and the localisation of TRAF1 to the proximal tubular epithelium from which many RCC originate, may indicate a potential for targeted therapy in RCC.
Keyword Apoptosis
Molecular marker
Renal cell carcinoma
siRNA
Traf
Tumour necrosis factor
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 7 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 10 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 02 Sep 2012, 00:15:55 EST by System User on behalf of School of Medicine