Upregulation of GRP78 in Renal Cell Carcinoma and Its Significance

被引:36
作者
Fu, Weijin [1 ]
Wu, Xiaoyun
Li, Jiachu
Mo, Zengnan
Yang, Zhanbing
Huang, Weihua
Ding, Qiang
机构
[1] Guangxi Med Univ, Dept Urol, Affiliated Hosp 1, Nanning, Guangxi, Peoples R China
关键词
ENDOPLASMIC-RETICULUM; PROTEIN GRP78; PROSTATE-CANCER; STRESS-RESPONSE; POOR-PROGNOSIS; ER STRESS; EXPRESSION; METASTASIS; ACTIVATION; APOPTOSIS;
D O I
10.1016/j.urology.2009.05.007
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVES To investigate the expression of GRP78 in human renal cell carcinoma (RCC) and its significance. METHODS We studied RNA and tissue section of a tumor and adjacent nontumorous renal tissues obtained from radical nephrectomy specimens of 42 patients and RCC cell lines. We used reverse transcriptase-PCR and immunohistochemistry to detect the GRP78 mRNA and protein expression, respectively. RESULTS Reverse transcriptase-PCR revealed that GRP78 mRNA is positively expressed in RCC cell lines (786-0, OS-RC-2, and Caki-1); the GRP78 mRNA expression in the RCC and adjacent nontumorous renal tissues was 0.88 +/- 0.34 and 0.44 +/- 0.15, respectively (P < .001). The GRP78 protein was found in RCC cell lines. Immunohistochemistry results also showed that the level of GRP78 protein expression of RCC tissues was significantly higher than that of the adjacent nontumorous renal tissues (P < .001). The high levels of GRP78 mRNA and protein expression were related to the large tumor size and high clinical stage (P < .001) but not to sex, age, and cell differentiate (P < .05). CONCLUSIONS To our knowledge, the present study is the first to report the upregulated expression of GRP78 and that it is possibly involved in pathogenesis of RCC. UROLOGY 75: 603-607, 2010. (C) 2010 Elsevier Inc.
引用
收藏
页码:603 / 607
页数:5
相关论文
共 30 条
[11]   Genetic basis of cancer of the kidney: Disease specific approaches to therapy [J].
Linehan, WM ;
Vasselli, J ;
Srinivasan, R ;
Walther, MM ;
Merino, M ;
Choyke, P ;
Vocke, C ;
Schmidt, L ;
Isaacs, JS ;
Glenn, G ;
Toro, J ;
Zbar, B ;
Bottaro, D ;
Neckers, L .
CLINICAL CANCER RESEARCH, 2004, 10 (18) :6282S-6289S
[12]  
Little Edward, 1994, Critical Reviews in Eukaryotic Gene Expression, V4, P1
[13]   Vascular endothelial growth factor-C-mediated lymphangiogenesis promotes tumour metastasis [J].
Mandriota, SJ ;
Jussila, L ;
Jeltsch, M ;
Compagni, A ;
Baetens, D ;
Prevo, R ;
Banerji, S ;
Huarte, J ;
Montesano, R ;
Jackson, DG ;
Orci, L ;
Alitalo, K ;
Christofori, G ;
Pepper, MS .
EMBO JOURNAL, 2001, 20 (04) :672-682
[14]   Gene silencing in mammals by small interfering RNAs [J].
McManus, MT ;
Sharp, PA .
NATURE REVIEWS GENETICS, 2002, 3 (10) :737-747
[15]   Translocation of bim to the endoplasmic reticulum (ER) mediates ER stress signaling for activation of caspase-12 during ER stress-induced apoptosis [J].
Morishima, N ;
Nakanishi, K ;
Tsuchiya, K ;
Shibata, T ;
Seiwa, E .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (48) :50375-50381
[16]   Systemic therapy for renal cell carcinoma [J].
Motzer, RJ ;
Russo, P .
JOURNAL OF UROLOGY, 2000, 163 (02) :408-417
[17]   Lymphatic metastasis in the absence of functional intratumor lymphatics [J].
Padera, TP ;
Kadambi, A ;
di Tomaso, E ;
Carreira, CM ;
Brown, EB ;
Boucher, Y ;
Choi, NC ;
Mathisen, D ;
Wain, J ;
Mark, EJ ;
Munn, LL ;
Jain, RK .
SCIENCE, 2002, 296 (5574) :1883-1886
[18]   Expression of stress response protein Grp78 is associated with the development of castration-resistant prostate cancer [J].
Pootrakul, Llana ;
Datar, Ram H. ;
Shi, Shan-Rong ;
Cai, Jie ;
Hawes, Debra ;
Groshen, Susan G. ;
Lee, Amy S. ;
Cote, Richard J. .
CLINICAL CANCER RESEARCH, 2006, 12 (20) :5987-5993
[19]   Endoplasmic reticulum chaperone protein GRP78 protects cells from apoptosis induced by topoisomerase inhibitors - Role of ATP binding site in suppression of caspase-7 activation [J].
Reddy, RK ;
Mao, CH ;
Baumeister, P ;
Austin, RC ;
Kaufman, RJ ;
Lee, AS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (23) :20915-20924
[20]   Small interference RNA targeting heat-shock protein 27 inhibits the growth of prostatic cell lines and induces apoptosis via caspase-3 activation in vitro [J].
Rocchi, Palma ;
Jugpal, Paul ;
So, Alan ;
Sinneman, Shannon ;
Ettinger, Susan ;
Fazli, Ladan ;
Nelson, Colleen ;
Gleave, Martin .
BJU INTERNATIONAL, 2006, 98 (05) :1082-1089