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Published in: Virchows Archiv 4/2013

01-04-2013 | Original Article

Low RKIP expression associates with poor prognosis in bladder cancer patients

Authors: Julieta Afonso, Adhemar Longatto-Filho, Olga Martinho, Francisco Lobo, Teresina Amaro, Rui M. Reis, Lúcio L. Santos

Published in: Virchows Archiv | Issue 4/2013

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Abstract

Urothelial bladder cancer (UBC) is a heterogeneous type of disease. It is urgent to screen biomarkers of tumour aggressiveness in order to clarify the clinical behaviour and to personalize therapy in UBC patients. Raf kinase inhibitory protein (RKIP) is a metastasis suppressor, and its downregulation is associated with metastatic events in an increasing number of solid tumours. We evaluated the clinical and prognostic significance of RKIP expression in patients with high risk of progression UBC. Using immunohistochemistry, we determined RKIP expression levels in a series of 81 patients with high-grade pT1/pTis or muscle-invasive UBC. Staining of CD31 and D2-40 was used to assess blood and lymphatic vessels, in order to distinguish between blood and lymphatic vessel invasion (LVI). We found that 90 % of pT1/pTis tumours, 94 % of non-muscle invasive papillary tumours and 76 % of the cases without LVI occurrence expressed RKIP in >10 % of cells. In this group, we observed a subgroup of tumours (42 %) in which the tumour centre was significantly more intensely stained than the invasion front. This heterogeneous pattern was observed in 63 % of the cases with LVI. Low RKIP expression was associated with poorer 5-year disease-free and overall survival rates, and remained as an independent prognostic factor for disease-free survival. Loss of RKIP expression may be an important prognostic factor for patients with high risk of progression bladder cancer.
Literature
2.
go back to reference Sternberg CN, Donat SM, Bellmunt J et al (2007) Chemotherapy for bladder cancer: treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer. Urology 69(Suppl 1):62–79PubMedCrossRef Sternberg CN, Donat SM, Bellmunt J et al (2007) Chemotherapy for bladder cancer: treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer. Urology 69(Suppl 1):62–79PubMedCrossRef
3.
go back to reference Sternberg CN (2006) Muscle invasive and metastatic bladder cancer. Ann Oncol 17(Suppl 10):23–30CrossRef Sternberg CN (2006) Muscle invasive and metastatic bladder cancer. Ann Oncol 17(Suppl 10):23–30CrossRef
4.
go back to reference Dhillon AS, Hagan S, Rath O, Kolch W (2007) MAP kinase signalling pathways in cancer. Oncogene 26:3279–3290PubMedCrossRef Dhillon AS, Hagan S, Rath O, Kolch W (2007) MAP kinase signalling pathways in cancer. Oncogene 26:3279–3290PubMedCrossRef
5.
go back to reference Davies H, Bignell GR, Cox C et al (2002) Mutations of the BRAF gene in human cancer. Nature 417:949–954PubMedCrossRef Davies H, Bignell GR, Cox C et al (2002) Mutations of the BRAF gene in human cancer. Nature 417:949–954PubMedCrossRef
6.
go back to reference Stoehr R, Brinkmann A, Filbeck T et al (2004) No evidence for mutation of B-RAF in urothelial carcinomas of the bladder and upper urinary tract. Oncol Rep 11(Suppl 1):137–141PubMed Stoehr R, Brinkmann A, Filbeck T et al (2004) No evidence for mutation of B-RAF in urothelial carcinomas of the bladder and upper urinary tract. Oncol Rep 11(Suppl 1):137–141PubMed
7.
go back to reference Boulalas I, Zaravinos A, Delakas D, Spandidos DA (2009) Mutational analysis of the BRAF gene in transitional cell carcinoma of the bladder. Int J Biol Markers 24(Suppl 1):17–21PubMed Boulalas I, Zaravinos A, Delakas D, Spandidos DA (2009) Mutational analysis of the BRAF gene in transitional cell carcinoma of the bladder. Int J Biol Markers 24(Suppl 1):17–21PubMed
8.
go back to reference Karlou M, Saetta AA, Korkolopoulou P et al (2009) Activation of extracellular regulated kinases (ERK1/2) predicts poor prognosis in urothelial bladder carcinoma and is not associated with B-Raf gene mutations. Pathology 41(Suppl 4):327–334PubMedCrossRef Karlou M, Saetta AA, Korkolopoulou P et al (2009) Activation of extracellular regulated kinases (ERK1/2) predicts poor prognosis in urothelial bladder carcinoma and is not associated with B-Raf gene mutations. Pathology 41(Suppl 4):327–334PubMedCrossRef
9.
go back to reference Zaravinos A, Chatziioannou M, Lambrou GI et al (2011) Implication of RAF and RKIP genes in urinary bladder cancer. Pathol Oncol Res 17(Suppl2): 181–190 Zaravinos A, Chatziioannou M, Lambrou GI et al (2011) Implication of RAF and RKIP genes in urinary bladder cancer. Pathol Oncol Res 17(Suppl2): 181–190
10.
go back to reference Klysik J, Theroux SJ, Sedivy JM, Moffit JS, Boekelheide K (2008) Signaling crossroads: the function of Raf kinase inhibitory protein in cancer, the central nervous system and reproduction. Cell Signal 20:1–9PubMedCrossRef Klysik J, Theroux SJ, Sedivy JM, Moffit JS, Boekelheide K (2008) Signaling crossroads: the function of Raf kinase inhibitory protein in cancer, the central nervous system and reproduction. Cell Signal 20:1–9PubMedCrossRef
11.
go back to reference Hellmann J, Rommelspacher H, Mühlbauer E, Wernicke C (2010) Raf kinase inhibitor protein enhances neuronal differentiation in human SH-SY5Y cells. Dev Neurosci 32(1):33–46PubMedCrossRef Hellmann J, Rommelspacher H, Mühlbauer E, Wernicke C (2010) Raf kinase inhibitor protein enhances neuronal differentiation in human SH-SY5Y cells. Dev Neurosci 32(1):33–46PubMedCrossRef
12.
go back to reference Eves EM, Shapiro P, Naik K et al (2006) Raf kinase inhibitory protein regulates aurora B kinase and the spindle checkpoint. Mol Cell 23(4):561–574PubMedCrossRef Eves EM, Shapiro P, Naik K et al (2006) Raf kinase inhibitory protein regulates aurora B kinase and the spindle checkpoint. Mol Cell 23(4):561–574PubMedCrossRef
13.
go back to reference Al-Mulla F, Bitar MS, Taqi Z, Rath O, Kolch W (2011) RAF kinase inhibitory protein (RKIP) modulates cell cycle kinetics and motility. Mol Biosyst 7(3):928–941PubMedCrossRef Al-Mulla F, Bitar MS, Taqi Z, Rath O, Kolch W (2011) RAF kinase inhibitory protein (RKIP) modulates cell cycle kinetics and motility. Mol Biosyst 7(3):928–941PubMedCrossRef
14.
go back to reference Yeung KC, Rose DW, Dhillon AS et al (2001) Raf kinase inhibitor protein interacts witw NF-kappaB-inducing kinase and TAK1 and inhibits NF-kappaB activation. Mol Cell Biol 21:7207–7217PubMedCrossRef Yeung KC, Rose DW, Dhillon AS et al (2001) Raf kinase inhibitor protein interacts witw NF-kappaB-inducing kinase and TAK1 and inhibits NF-kappaB activation. Mol Cell Biol 21:7207–7217PubMedCrossRef
15.
go back to reference Kim SY, Park SG, Jung H et al (2011) RKIP downregulation induces the HBx-mediated Raf-1 mitochondrial translocation. J Microbiol Biotechnol 21(5):525–528PubMedCrossRef Kim SY, Park SG, Jung H et al (2011) RKIP downregulation induces the HBx-mediated Raf-1 mitochondrial translocation. J Microbiol Biotechnol 21(5):525–528PubMedCrossRef
16.
go back to reference Baritaki S, Chapman A, Yeung K et al (2009) Inhibition of epithelial to mesenchymal transition in metastatic prostate cancer cells by the novel proteasome inhibitor, NPI-0052: pivotal roles of Snail repression and RKIP induction. Oncogene 28(40):3573–3485PubMedCrossRef Baritaki S, Chapman A, Yeung K et al (2009) Inhibition of epithelial to mesenchymal transition in metastatic prostate cancer cells by the novel proteasome inhibitor, NPI-0052: pivotal roles of Snail repression and RKIP induction. Oncogene 28(40):3573–3485PubMedCrossRef
17.
go back to reference Wu K, Bonavida B (2009) The activated NF-kappaB-Snail-RKIP circuitry in cancer regulates both the metastatic cascade and resistance to apoptosis by cytotoxic drugs. Crit Rev Immunol 29(3):241–254PubMedCrossRef Wu K, Bonavida B (2009) The activated NF-kappaB-Snail-RKIP circuitry in cancer regulates both the metastatic cascade and resistance to apoptosis by cytotoxic drugs. Crit Rev Immunol 29(3):241–254PubMedCrossRef
18.
go back to reference Zhu S, Mc Henry KT, Lane WS, Fenteany G (2005) A chemical inhibitor reveals the role of Raf kinase inhibitor protein in cell migration. Chem Biol 12(9):981–991PubMedCrossRef Zhu S, Mc Henry KT, Lane WS, Fenteany G (2005) A chemical inhibitor reveals the role of Raf kinase inhibitor protein in cell migration. Chem Biol 12(9):981–991PubMedCrossRef
19.
go back to reference Yeung K, Janosch P, McFerran B et al (2000) Mechanism of suppression of the Raf/MEK/extracellular signal-regulated kinase pathway by the raf kinase inhibitor protein. Mol Cell Biol 20(9):3079–3085PubMedCrossRef Yeung K, Janosch P, McFerran B et al (2000) Mechanism of suppression of the Raf/MEK/extracellular signal-regulated kinase pathway by the raf kinase inhibitor protein. Mol Cell Biol 20(9):3079–3085PubMedCrossRef
20.
go back to reference Tang H, Park S, Sun SC et al (2010) RKIP inhibits NF-kappaB in cancer cells by regulating upstream signaling components of the IkappaB kinase complex. FEBS Lett 584(4):662–668PubMedCrossRef Tang H, Park S, Sun SC et al (2010) RKIP inhibits NF-kappaB in cancer cells by regulating upstream signaling components of the IkappaB kinase complex. FEBS Lett 584(4):662–668PubMedCrossRef
21.
go back to reference Lorenz K, Lohse MJ, Quitterer U et al (2003) Protein kinase C switches the Raf kinase inhibitor from Raf-1 to GRK-2. Nature 426:574–579PubMedCrossRef Lorenz K, Lohse MJ, Quitterer U et al (2003) Protein kinase C switches the Raf kinase inhibitor from Raf-1 to GRK-2. Nature 426:574–579PubMedCrossRef
22.
go back to reference Al-Mulla F, Bitar MS, Al-Maghrebi M et al (2011) Raf kinase inhibitor protein RKIP enhances signaling by glycogen synthase kinase-3β. Cancer Res 71(4):1334–1343PubMedCrossRef Al-Mulla F, Bitar MS, Al-Maghrebi M et al (2011) Raf kinase inhibitor protein RKIP enhances signaling by glycogen synthase kinase-3β. Cancer Res 71(4):1334–1343PubMedCrossRef
23.
go back to reference Fu Z, Smith PC, Zhang L (2003) Effects of raf kinase inhibitor protein expression on suppression of prostate cancer metastasis. J Natl Cancer Inst 95:878–879PubMedCrossRef Fu Z, Smith PC, Zhang L (2003) Effects of raf kinase inhibitor protein expression on suppression of prostate cancer metastasis. J Natl Cancer Inst 95:878–879PubMedCrossRef
24.
go back to reference Hagan S, Al-Mulla F, Mallon E (2005) Reduction of Raf-1 kinase inhibitor protein expression correlates with breast cancer metastasis. Clin Cancer Res 11:7392–7397PubMedCrossRef Hagan S, Al-Mulla F, Mallon E (2005) Reduction of Raf-1 kinase inhibitor protein expression correlates with breast cancer metastasis. Clin Cancer Res 11:7392–7397PubMedCrossRef
25.
go back to reference Al-Mulla F, Hagan S, Behbehani AI (2006) Raf kinase inhibitor protein expression in a survival analysis of colorectal cancer patients. J Clin Oncol 24:5672–5679PubMedCrossRef Al-Mulla F, Hagan S, Behbehani AI (2006) Raf kinase inhibitor protein expression in a survival analysis of colorectal cancer patients. J Clin Oncol 24:5672–5679PubMedCrossRef
26.
go back to reference Schuierer MM, Bataille F, Hagan S, Kolch W, Bosserhoff AK (2004) Reduction of Raf kinase inhibitor protein expression is associated with increased Ras-extracellular signal-regulated kinase signaling in melanoma cell lines. Cancer Res 64:5186–5192PubMedCrossRef Schuierer MM, Bataille F, Hagan S, Kolch W, Bosserhoff AK (2004) Reduction of Raf kinase inhibitor protein expression is associated with increased Ras-extracellular signal-regulated kinase signaling in melanoma cell lines. Cancer Res 64:5186–5192PubMedCrossRef
27.
go back to reference Afonso J, Santos LL, Amaro T, Lobo F, Longatto-Filho A (2009) The aggressiveness of urothelial carcinoma depends to a large extent on lymphovascular invasion—the prognostic contribution of related molecular markers. Histopathology 55:514–524PubMedCrossRef Afonso J, Santos LL, Amaro T, Lobo F, Longatto-Filho A (2009) The aggressiveness of urothelial carcinoma depends to a large extent on lymphovascular invasion—the prognostic contribution of related molecular markers. Histopathology 55:514–524PubMedCrossRef
28.
go back to reference Amin MB, Srigley JR, Grignon DJ et al (2005) Urinary bladder cancer protocols and checklists. College of American Pathologists, Northfield Amin MB, Srigley JR, Grignon DJ et al (2005) Urinary bladder cancer protocols and checklists. College of American Pathologists, Northfield
29.
go back to reference Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A (2010) AJCC cancer staging manual. Springer, New York Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A (2010) AJCC cancer staging manual. Springer, New York
30.
go back to reference Mostofi CJ, Davis CJ, Sesterhenn IA (1999) World Health Organization, International Histological Classification of Tumours. Histological typing of urinary bladder tumours. Springer, BerlinCrossRef Mostofi CJ, Davis CJ, Sesterhenn IA (1999) World Health Organization, International Histological Classification of Tumours. Histological typing of urinary bladder tumours. Springer, BerlinCrossRef
31.
go back to reference Eble JN, Sauter G, Epstein JI, Sesterhenn IA (2004) World Health Organization Classification of Tumours. Pathology and genetics of tumours of the urinary system and male genital organ. IARC Press, Lyon Eble JN, Sauter G, Epstein JI, Sesterhenn IA (2004) World Health Organization Classification of Tumours. Pathology and genetics of tumours of the urinary system and male genital organ. IARC Press, Lyon
32.
go back to reference Martinho O, Gouveia A, Silva P et al (2009) Loss of RKIP expression is associated with poor survival in GISTs. Virchows Arch 455(Suppl 3):277–284PubMedCrossRef Martinho O, Gouveia A, Silva P et al (2009) Loss of RKIP expression is associated with poor survival in GISTs. Virchows Arch 455(Suppl 3):277–284PubMedCrossRef
33.
go back to reference Martinho O, Faloppa CC, Neto CS et al (2012) Loss of RKIP expression during the carcinogenic evolution of endometrial cancer. J Clin Pathol 65(Suppl 2):122–128PubMedCrossRef Martinho O, Faloppa CC, Neto CS et al (2012) Loss of RKIP expression during the carcinogenic evolution of endometrial cancer. J Clin Pathol 65(Suppl 2):122–128PubMedCrossRef
34.
go back to reference Martinho O, Granja S, Jaraquemada T et al (2012) Downregulation of RKIP is associated with poor outcome and malignant progression in gliomas. PLoS One 7(1):e30769PubMedCrossRef Martinho O, Granja S, Jaraquemada T et al (2012) Downregulation of RKIP is associated with poor outcome and malignant progression in gliomas. PLoS One 7(1):e30769PubMedCrossRef
35.
go back to reference Bevilacqua E, Frankenberger CA, Rosner MR (2012) RKIP suppresses breast cancer metastasis to the bone by regulating stroma-associated genes. Int J Breast Cancer 2012:124704PubMed Bevilacqua E, Frankenberger CA, Rosner MR (2012) RKIP suppresses breast cancer metastasis to the bone by regulating stroma-associated genes. Int J Breast Cancer 2012:124704PubMed
36.
go back to reference Hao C, Wei S, Tong Z et al (2012) The effects of RKIP gene expression on the biological characteristics of human triple-negative breast cancer cells in vitro. Tumour Biol 33(Suppl 4):1159–1167PubMedCrossRef Hao C, Wei S, Tong Z et al (2012) The effects of RKIP gene expression on the biological characteristics of human triple-negative breast cancer cells in vitro. Tumour Biol 33(Suppl 4):1159–1167PubMedCrossRef
37.
go back to reference Xinzhou H, Ning Y, Ou W et al (2011) RKIP inhibits the migration and invasion of human prostate cancer PC-3 M cells through regulation of extracellular matrix. Mol Biol (Mosk) 45(Suppl 6):1004–1011 Xinzhou H, Ning Y, Ou W et al (2011) RKIP inhibits the migration and invasion of human prostate cancer PC-3 M cells through regulation of extracellular matrix. Mol Biol (Mosk) 45(Suppl 6):1004–1011
38.
go back to reference Beshir AB, Ren G, Magpusao AN et al (2010) Raf kinase inhibitor protein suppresses nuclear factor-κB-dependent cancer cell invasion through negative regulation of matrix metalloproteinase expression. Cancer Lett 299(Suppl 2):137–149PubMedCrossRef Beshir AB, Ren G, Magpusao AN et al (2010) Raf kinase inhibitor protein suppresses nuclear factor-κB-dependent cancer cell invasion through negative regulation of matrix metalloproteinase expression. Cancer Lett 299(Suppl 2):137–149PubMedCrossRef
39.
go back to reference Beach S, Tang H, Park S et al (2008) Snail is a repressor of RKIP transcription in metastatic prostate cancer cells. Oncogene 27(Suppl 15):2243–2248PubMedCrossRef Beach S, Tang H, Park S et al (2008) Snail is a repressor of RKIP transcription in metastatic prostate cancer cells. Oncogene 27(Suppl 15):2243–2248PubMedCrossRef
40.
go back to reference Thuault S, Valcourt U, Petersen M et al (2006) Transforming growth factor-beta employs HMGA2 to elicit epithelial–mesenchymal transition. J Cell Biol 174(2):175–183PubMedCrossRef Thuault S, Valcourt U, Petersen M et al (2006) Transforming growth factor-beta employs HMGA2 to elicit epithelial–mesenchymal transition. J Cell Biol 174(2):175–183PubMedCrossRef
41.
go back to reference Lee YS, Dutta A (2007) The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. Genes Dev 21(9):1025–1030PubMedCrossRef Lee YS, Dutta A (2007) The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. Genes Dev 21(9):1025–1030PubMedCrossRef
42.
go back to reference Dangi-Garimella S, Yun J, Eves EM et al (2009) Raf kinase inhibitory protein suppresses a metastasis signalling cascade involving LIN28 and let-7. EMBO J 28(4):347–358PubMedCrossRef Dangi-Garimella S, Yun J, Eves EM et al (2009) Raf kinase inhibitory protein suppresses a metastasis signalling cascade involving LIN28 and let-7. EMBO J 28(4):347–358PubMedCrossRef
43.
go back to reference Yun J, Frankenberger CA, Kuo WL et al (2011) Signalling pathway for RKIP and Let-7 regulates and predicts metastatic breast cancer. EMBO J 30(21):4500–4514PubMedCrossRef Yun J, Frankenberger CA, Kuo WL et al (2011) Signalling pathway for RKIP and Let-7 regulates and predicts metastatic breast cancer. EMBO J 30(21):4500–4514PubMedCrossRef
44.
go back to reference Zhang L, Fu Z, Binkley C et al (2004) Raf kinase inhibitory protein inhibits beta-cell proliferation. Surgery 136:708–715PubMedCrossRef Zhang L, Fu Z, Binkley C et al (2004) Raf kinase inhibitory protein inhibits beta-cell proliferation. Surgery 136:708–715PubMedCrossRef
45.
go back to reference Li HZ, Wang Y, Gao Y et al (2008) Effects of raf kinase inhibitor protein expression on metastasis and progression of human epithelial ovarian cancer. Mol Cancer Res 6(Suppl 6):917–928PubMedCrossRef Li HZ, Wang Y, Gao Y et al (2008) Effects of raf kinase inhibitor protein expression on metastasis and progression of human epithelial ovarian cancer. Mol Cancer Res 6(Suppl 6):917–928PubMedCrossRef
46.
go back to reference Wang J, Yang YH, Wang AQ (2010) Immunohistochemical detection of the Raf kinase inhibitor protein in nonneoplastic gastric tissue and gastric cancer tissue. Med Oncol 27(Suppl 2):219–223PubMedCrossRef Wang J, Yang YH, Wang AQ (2010) Immunohistochemical detection of the Raf kinase inhibitor protein in nonneoplastic gastric tissue and gastric cancer tissue. Med Oncol 27(Suppl 2):219–223PubMedCrossRef
47.
go back to reference Lee HC, Tian B, Sedivy JM, Wands JR, Kim M (2006) Loss of Raf kinase inhibitor protein promotes cell proliferation and migration of human hepatoma cells. Gastroenterology 131(Suppl 4):1208–1217PubMedCrossRef Lee HC, Tian B, Sedivy JM, Wands JR, Kim M (2006) Loss of Raf kinase inhibitor protein promotes cell proliferation and migration of human hepatoma cells. Gastroenterology 131(Suppl 4):1208–1217PubMedCrossRef
48.
go back to reference Hu CJ, Zhou L, Zhang J, Huang C, Zhang GM (2011) Immunohistochemical detection of Raf kinase inhibitor protein in normal cervical tissue and cervical cancer tissue. J Int Med Res 39(Suppl 1):229–237PubMed Hu CJ, Zhou L, Zhang J, Huang C, Zhang GM (2011) Immunohistochemical detection of Raf kinase inhibitor protein in normal cervical tissue and cervical cancer tissue. J Int Med Res 39(Suppl 1):229–237PubMed
49.
go back to reference Kim HS, Won KY, Kim GY et al (2012) Reduced expression of Raf-1 kinase inhibitory protein predicts regional lymph node metastasis and shorter survival in esophageal squamous cell carcinoma. Pathol Res Pract 208(Suppl 5):292–299PubMedCrossRef Kim HS, Won KY, Kim GY et al (2012) Reduced expression of Raf-1 kinase inhibitory protein predicts regional lymph node metastasis and shorter survival in esophageal squamous cell carcinoma. Pathol Res Pract 208(Suppl 5):292–299PubMedCrossRef
50.
go back to reference Kim HS, Lee SH, Won KY (2012) Expression of Raf-1 kinase inhibitory protein in carcinoma of the ampulla of Vater. Virchows Arch 460(Suppl 1):61–68PubMedCrossRef Kim HS, Lee SH, Won KY (2012) Expression of Raf-1 kinase inhibitory protein in carcinoma of the ampulla of Vater. Virchows Arch 460(Suppl 1):61–68PubMedCrossRef
51.
go back to reference Fu Z, Kitagawa Y, Shen R et al (2006) Metastasis suppressor gene Raf kinase inhibitor protein (RKIP) is a novel prognostic marker in prostate cancer. Prostate 66:248–256PubMedCrossRef Fu Z, Kitagawa Y, Shen R et al (2006) Metastasis suppressor gene Raf kinase inhibitor protein (RKIP) is a novel prognostic marker in prostate cancer. Prostate 66:248–256PubMedCrossRef
52.
go back to reference Chatterjee D, Sabo E, Tavares R, Resnick MB (2008) Inverse association between Raf Kinase Inhibitory Protein and signal transducers and activators of transcription 3 expression in gastric adenocarcinoma patients: implications for clinical outcome. Clin Cancer Res 14(Suppl 10):2994–3001PubMedCrossRef Chatterjee D, Sabo E, Tavares R, Resnick MB (2008) Inverse association between Raf Kinase Inhibitory Protein and signal transducers and activators of transcription 3 expression in gastric adenocarcinoma patients: implications for clinical outcome. Clin Cancer Res 14(Suppl 10):2994–3001PubMedCrossRef
53.
go back to reference Gao C, Pang L, Ren C, Ma T (2012) Prognostic value of raf kinase inhibitor protein in esophageal squamous cell carcinoma. Pathol Oncol Res 18(Suppl 2):471–477PubMedCrossRef Gao C, Pang L, Ren C, Ma T (2012) Prognostic value of raf kinase inhibitor protein in esophageal squamous cell carcinoma. Pathol Oncol Res 18(Suppl 2):471–477PubMedCrossRef
54.
go back to reference Kim HS, Kim GY, Lim SJ, Kim YW (2010) Loss of Raf-1 kinase inhibitory protein in pancreatic ductal adenocarcinoma. Pathology 42(Suppl 7):655–660PubMedCrossRef Kim HS, Kim GY, Lim SJ, Kim YW (2010) Loss of Raf-1 kinase inhibitory protein in pancreatic ductal adenocarcinoma. Pathology 42(Suppl 7):655–660PubMedCrossRef
55.
go back to reference Kim HS, Kim GY, Lim SJ, Park YK, Kim YW (2010) Reduced expression of Raf-1 kinase inhibitory protein is a significant prognostic marker in patients with gallbladder carcinoma. Hum Pathol 41(Suppl 11):1609–1616PubMedCrossRef Kim HS, Kim GY, Lim SJ, Park YK, Kim YW (2010) Reduced expression of Raf-1 kinase inhibitory protein is a significant prognostic marker in patients with gallbladder carcinoma. Hum Pathol 41(Suppl 11):1609–1616PubMedCrossRef
56.
go back to reference Chatterjee D, Bai Y, Wang Z et al (2004) RKIP sensitizes prostate and breast cancer cells to drug-induced apoptosis. J Biol Chem 279(Suppl 17):17515–17523PubMedCrossRef Chatterjee D, Bai Y, Wang Z et al (2004) RKIP sensitizes prostate and breast cancer cells to drug-induced apoptosis. J Biol Chem 279(Suppl 17):17515–17523PubMedCrossRef
57.
go back to reference Ruan L, Wang GL, Yi H, Chen Y et al (2010) Raf kinase inhibitor protein correlates with sensitivity of nasopharyngeal carcinoma to radiotherapy. J Cell Biochem 110(Suppl 4):975–981PubMedCrossRef Ruan L, Wang GL, Yi H, Chen Y et al (2010) Raf kinase inhibitor protein correlates with sensitivity of nasopharyngeal carcinoma to radiotherapy. J Cell Biochem 110(Suppl 4):975–981PubMedCrossRef
58.
go back to reference Woods Ignatoski KM, Grewal NK, Markwart SM et al (2008) Loss of Raf kinase inhibitory protein induces radioresistance in prostate cancer. Int J Radiat Oncol Biol Phys 72(Suppl 1):153–160PubMedCrossRef Woods Ignatoski KM, Grewal NK, Markwart SM et al (2008) Loss of Raf kinase inhibitory protein induces radioresistance in prostate cancer. Int J Radiat Oncol Biol Phys 72(Suppl 1):153–160PubMedCrossRef
59.
go back to reference Al-Mulla F, Hagan S, Al-Ali W (2008) Raf kinase inhibitor protein: mechanism of loss of expression and association with genomic instability. J Clin Pathol 61(Suppl 4):524–529PubMedCrossRef Al-Mulla F, Hagan S, Al-Ali W (2008) Raf kinase inhibitor protein: mechanism of loss of expression and association with genomic instability. J Clin Pathol 61(Suppl 4):524–529PubMedCrossRef
60.
go back to reference Minoo P, Baker K, Goswami R (2006) Extensive DNA methylation in normal colorectal mucosa in hyperplastic polyposis. Gut 55(Suppl 10):1467–1474PubMedCrossRef Minoo P, Baker K, Goswami R (2006) Extensive DNA methylation in normal colorectal mucosa in hyperplastic polyposis. Gut 55(Suppl 10):1467–1474PubMedCrossRef
61.
go back to reference Ren G, Baritaki S, Marathe H et al (2012) Polycomb protein EZH2 regulates tumor invasion via the transcriptional repression of the metastasis suppressor RKIP in breast and prostate cancer. Cancer Res 72(12):3091–3104PubMedCrossRef Ren G, Baritaki S, Marathe H et al (2012) Polycomb protein EZH2 regulates tumor invasion via the transcriptional repression of the metastasis suppressor RKIP in breast and prostate cancer. Cancer Res 72(12):3091–3104PubMedCrossRef
62.
go back to reference Al-Mulla F, Bitar MS, Feng J, Park S, Yeung KC (2012) A new model for raf kinase inhibitory protein induced chemotherapeutic resistance. PLoS One 7(1):e29532PubMedCrossRef Al-Mulla F, Bitar MS, Feng J, Park S, Yeung KC (2012) A new model for raf kinase inhibitory protein induced chemotherapeutic resistance. PLoS One 7(1):e29532PubMedCrossRef
Metadata
Title
Low RKIP expression associates with poor prognosis in bladder cancer patients
Authors
Julieta Afonso
Adhemar Longatto-Filho
Olga Martinho
Francisco Lobo
Teresina Amaro
Rui M. Reis
Lúcio L. Santos
Publication date
01-04-2013
Publisher
Springer-Verlag
Published in
Virchows Archiv / Issue 4/2013
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-013-1388-2

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