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Published in: BMC Cancer 1/2011

Open Access 01-12-2011 | Research article

Expression of phosphorylated raf kinase inhibitor protein (pRKIP) is a predictor of lung cancer survival

Authors: Sara Huerta-Yepez, Nam K Yoon, Angeles Hernandez-Cueto, Vei Mah, Clara M Rivera-Pazos, Devasis Chatterjee, Mario I Vega, Erin L Maresh, Steve Horvath, David Chia, Benjamin Bonavida, Lee Goodglick

Published in: BMC Cancer | Issue 1/2011

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Abstract

Background

Raf-1 kinase inhibitor protein (RKIP) has been reported to negatively regulate signal kinases of major survival pathways. RKIP activity is modulated in part by phosphorylation on Serine 153 by protein kinase C, which leads to dissociation of RKIP from Raf-1. RKIP expression is low in many human cancers and represents an indicator of poor prognosis and/or induction of metastasis. The prognostic power has typically been based on total RKIP expression and has not considered the significance of phospho-RKIP.

Methods

The present study examined the expression levels of both RKIP and phospho-RKIP in human lung cancer tissue microarray proteomics technology.

Results

Total RKIP and phospho-RKIP expression levels were similar in normal and cancerous tissues. phospho-RKIP levels slightly decreased in metastatic lesions. However, the expression levels of phospho-RKIP, in contrast to total RKIP, displayed significant predictive power for outcome with normal expression of phospho-RKIP predicting a more favorable survival compared to lower levels (P = 0.0118); this was even more pronounced in more senior individuals and in those with early stage lung cancer.

Conclusions

This study examines for the first time, the expression profile of RKIP and phospho-RKIP in lung cancer. Significantly, we found that phospho-RKIP was a predictive indicator of survival.
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Literature
1.
go back to reference Yeung K, Seitz T, Li S, Janosch P, McFerran B, Kaiser C, Fee F, Katsanakis KD, Rose DW, Mischak H, Sedivy JM, Kolch W: Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP. Nature. 1999, 401 (6749): 173-177. 10.1038/43686.CrossRefPubMed Yeung K, Seitz T, Li S, Janosch P, McFerran B, Kaiser C, Fee F, Katsanakis KD, Rose DW, Mischak H, Sedivy JM, Kolch W: Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP. Nature. 1999, 401 (6749): 173-177. 10.1038/43686.CrossRefPubMed
2.
go back to reference Yeung K, Janosch P, McFerran B, Rose DW, Mischak H, Sedivy JM, Kolch W: Mechanism of suppression of the Raf/MEK/extracellular signal-regulated kinase pathway by the raf kinase inhibitor protein. Molecular and cellular biology. 2000, 20 (9): 3079-3085. 10.1128/MCB.20.9.3079-3085.2000.CrossRefPubMedPubMedCentral Yeung K, Janosch P, McFerran B, Rose DW, Mischak H, Sedivy JM, Kolch W: Mechanism of suppression of the Raf/MEK/extracellular signal-regulated kinase pathway by the raf kinase inhibitor protein. Molecular and cellular biology. 2000, 20 (9): 3079-3085. 10.1128/MCB.20.9.3079-3085.2000.CrossRefPubMedPubMedCentral
3.
go back to reference Yeung KC, Rose DW, Dhillon AS, Yaros D, Gustafsson M, Chatterjee D, McFerran B, Wyche J, Kolch W, Sedivy JM: Raf kinase inhibitor protein interacts with NF-kappaB-inducing kinase and TAK1 and inhibits NF-kappaB activation. Molecular and cellular biology. 2001, 21 (21): 7207-7217. 10.1128/MCB.21.21.7207-7217.2001.CrossRefPubMedPubMedCentral Yeung KC, Rose DW, Dhillon AS, Yaros D, Gustafsson M, Chatterjee D, McFerran B, Wyche J, Kolch W, Sedivy JM: Raf kinase inhibitor protein interacts with NF-kappaB-inducing kinase and TAK1 and inhibits NF-kappaB activation. Molecular and cellular biology. 2001, 21 (21): 7207-7217. 10.1128/MCB.21.21.7207-7217.2001.CrossRefPubMedPubMedCentral
4.
go back to reference Granovsky AE, Rosner MR: Raf kinase inhibitory protein: a signal transduction modulator and metastasis suppressor. Cell research. 2008, 18 (4): 452-457. 10.1038/cr.2008.43.CrossRefPubMed Granovsky AE, Rosner MR: Raf kinase inhibitory protein: a signal transduction modulator and metastasis suppressor. Cell research. 2008, 18 (4): 452-457. 10.1038/cr.2008.43.CrossRefPubMed
5.
go back to reference Fu Z, Kitagawa Y, Shen R, Shah R, Mehra R, Rhodes D, Keller PJ, Mizokami A, Dunn R, Chinnaiyan AM, Yao Z, Keller ET: Metastasis suppressor gene Raf kinase inhibitor protein (RKIP) is a novel prognostic marker in prostate cancer. The Prostate. 2006, 66 (3): 248-256. 10.1002/pros.20319.CrossRefPubMed Fu Z, Kitagawa Y, Shen R, Shah R, Mehra R, Rhodes D, Keller PJ, Mizokami A, Dunn R, Chinnaiyan AM, Yao Z, Keller ET: Metastasis suppressor gene Raf kinase inhibitor protein (RKIP) is a novel prognostic marker in prostate cancer. The Prostate. 2006, 66 (3): 248-256. 10.1002/pros.20319.CrossRefPubMed
6.
go back to reference Fu Z, Smith PC, Zhang L, Rubin MA, Dunn RL, Yao Z, Keller ET: Effects of raf kinase inhibitor protein expression on suppression of prostate cancer metastasis. Journal of the National Cancer Institute. 2003, 95 (12): 878-889. 10.1093/jnci/95.12.878.CrossRefPubMed Fu Z, Smith PC, Zhang L, Rubin MA, Dunn RL, Yao Z, Keller ET: Effects of raf kinase inhibitor protein expression on suppression of prostate cancer metastasis. Journal of the National Cancer Institute. 2003, 95 (12): 878-889. 10.1093/jnci/95.12.878.CrossRefPubMed
7.
go back to reference Chatterjee D, Bai Y, Wang Z, Beach S, Mott S, Roy R, Braastad C, Sun Y, Mukhopadhyay A, Aggarwal BB, Darnowski J, Pantazis P, Wyche J, Fu Z, Kitagwa Y, Keller ET, Sedivy JM, Yeung KC: RKIP sensitizes prostate and breast cancer cells to drug-induced apoptosis. The Journal of biological chemistry. 2004, 279 (17): 17515-17523. 10.1074/jbc.M313816200.CrossRefPubMed Chatterjee D, Bai Y, Wang Z, Beach S, Mott S, Roy R, Braastad C, Sun Y, Mukhopadhyay A, Aggarwal BB, Darnowski J, Pantazis P, Wyche J, Fu Z, Kitagwa Y, Keller ET, Sedivy JM, Yeung KC: RKIP sensitizes prostate and breast cancer cells to drug-induced apoptosis. The Journal of biological chemistry. 2004, 279 (17): 17515-17523. 10.1074/jbc.M313816200.CrossRefPubMed
8.
go back to reference Baritaki S, Katsman A, Chatterjee D, Yeung KC, Spandidos DA, Bonavida B: Regulation of tumor cell sensitivity to TRAIL-induced apoptosis by the metastatic suppressor Raf kinase inhibitor protein via Yin Yang 1 inhibition and death receptor 5 up-regulation. J Immunol. 2007, 179 (8): 5441-5453.CrossRefPubMed Baritaki S, Katsman A, Chatterjee D, Yeung KC, Spandidos DA, Bonavida B: Regulation of tumor cell sensitivity to TRAIL-induced apoptosis by the metastatic suppressor Raf kinase inhibitor protein via Yin Yang 1 inhibition and death receptor 5 up-regulation. J Immunol. 2007, 179 (8): 5441-5453.CrossRefPubMed
9.
go back to reference Hagan S, Al-Mulla F, Mallon E, Oien K, Ferrier R, Gusterson B, Garcia JJ, Kolch W: Reduction of Raf-1 kinase inhibitor protein expression correlates with breast cancer metastasis. Clin Cancer Res. 2005, 11 (20): 7392-7397. 10.1158/1078-0432.CCR-05-0283.CrossRefPubMed Hagan S, Al-Mulla F, Mallon E, Oien K, Ferrier R, Gusterson B, Garcia JJ, Kolch W: Reduction of Raf-1 kinase inhibitor protein expression correlates with breast cancer metastasis. Clin Cancer Res. 2005, 11 (20): 7392-7397. 10.1158/1078-0432.CCR-05-0283.CrossRefPubMed
10.
go back to reference Al-Mulla F, Hagan S, Behbehani AI, Bitar MS, George SS, Going JJ, Garcia JJ, Scott L, Fyfe N, Murray GI, Kolch W: Raf kinase inhibitor protein expression in a survival analysis of colorectal cancer patients. J Clin Oncol. 2006, 24 (36): 5672-5679. 10.1200/JCO.2006.07.5499.CrossRefPubMed Al-Mulla F, Hagan S, Behbehani AI, Bitar MS, George SS, Going JJ, Garcia JJ, Scott L, Fyfe N, Murray GI, Kolch W: Raf kinase inhibitor protein expression in a survival analysis of colorectal cancer patients. J Clin Oncol. 2006, 24 (36): 5672-5679. 10.1200/JCO.2006.07.5499.CrossRefPubMed
11.
go back to reference Schuierer MM, Bataille F, Weiss TS, Hellerbrand C, Bosserhoff AK: Raf kinase inhibitor protein is downregulated in hepatocellular carcinoma. Oncology reports. 2006, 16 (3): 451-456.PubMed Schuierer MM, Bataille F, Weiss TS, Hellerbrand C, Bosserhoff AK: Raf kinase inhibitor protein is downregulated in hepatocellular carcinoma. Oncology reports. 2006, 16 (3): 451-456.PubMed
12.
go back to reference Chatterjee D, Sabo E, Tavares R, Resnick MB: 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. 2008, 14 (10): 2994-3001. 10.1158/1078-0432.CCR-07-4496.CrossRefPubMed Chatterjee D, Sabo E, Tavares R, Resnick MB: 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. 2008, 14 (10): 2994-3001. 10.1158/1078-0432.CCR-07-4496.CrossRefPubMed
13.
go back to reference Minoo P, Zlobec I, Baker K, Tornillo L, Terracciano L, Jass JR, Lugli A: Loss of raf-1 kinase inhibitor protein expression is associated with tumor progression and metastasis in colorectal cancer. American journal of clinical pathology. 2007, 127 (5): 820-827. 10.1309/5D7MM22DAVGDT1R8.CrossRefPubMed Minoo P, Zlobec I, Baker K, Tornillo L, Terracciano L, Jass JR, Lugli A: Loss of raf-1 kinase inhibitor protein expression is associated with tumor progression and metastasis in colorectal cancer. American journal of clinical pathology. 2007, 127 (5): 820-827. 10.1309/5D7MM22DAVGDT1R8.CrossRefPubMed
14.
go back to reference Peinado H, Olmeda D, Cano A: Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype?. Nature reviews. 2007, 7 (6): 415-428.PubMed Peinado H, Olmeda D, Cano A: Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype?. Nature reviews. 2007, 7 (6): 415-428.PubMed
15.
go back to reference Moreno-Bueno G, Portillo F, Cano A: Transcriptional regulation of cell polarity in EMT and cancer. Oncogene. 2008, 27 (55): 6958-6969. 10.1038/onc.2008.346.CrossRefPubMed Moreno-Bueno G, Portillo F, Cano A: Transcriptional regulation of cell polarity in EMT and cancer. Oncogene. 2008, 27 (55): 6958-6969. 10.1038/onc.2008.346.CrossRefPubMed
16.
go back to reference Beach S, Tang H, Park S, Dhillon AS, Keller ET, Kolch W, Yeung KC: Snail is a repressor of RKIP transcription in metastatic prostate cancer cells. Oncogene. 2008, 27 (15): 2243-2248. 10.1038/sj.onc.1210860.CrossRefPubMed Beach S, Tang H, Park S, Dhillon AS, Keller ET, Kolch W, Yeung KC: Snail is a repressor of RKIP transcription in metastatic prostate cancer cells. Oncogene. 2008, 27 (15): 2243-2248. 10.1038/sj.onc.1210860.CrossRefPubMed
17.
go back to reference Corbit KC, Trakul N, Eves EM, Diaz B, Marshall M, Rosner MR: Activation of Raf-1 signaling by protein kinase C through a mechanism involving Raf kinase inhibitory protein. The Journal of biological chemistry. 2003, 278 (15): 13061-13068. 10.1074/jbc.M210015200.CrossRefPubMed Corbit KC, Trakul N, Eves EM, Diaz B, Marshall M, Rosner MR: Activation of Raf-1 signaling by protein kinase C through a mechanism involving Raf kinase inhibitory protein. The Journal of biological chemistry. 2003, 278 (15): 13061-13068. 10.1074/jbc.M210015200.CrossRefPubMed
18.
go back to reference Lorenz K, Lohse MJ, Quitterer U: Protein kinase C switches the Raf kinase inhibitor from Raf-1 to GRK-2. Nature. 2003, 426 (6966): 574-579. 10.1038/nature02158.CrossRefPubMed Lorenz K, Lohse MJ, Quitterer U: Protein kinase C switches the Raf kinase inhibitor from Raf-1 to GRK-2. Nature. 2003, 426 (6966): 574-579. 10.1038/nature02158.CrossRefPubMed
19.
go back to reference Mah V, Seligson DB, Li A, Marquez DC, Elshimali Y, Fishbein MC, Chia D, Pietras RJ, Goodglick L: Aromatase expression predicts survival in women with early-stage non small cell lung cancer. Cancer research. 2007, 67 (21): 10484-10490. 10.1158/0008-5472.CAN-07-2607.CrossRefPubMedPubMedCentral Mah V, Seligson DB, Li A, Marquez DC, Elshimali Y, Fishbein MC, Chia D, Pietras RJ, Goodglick L: Aromatase expression predicts survival in women with early-stage non small cell lung cancer. Cancer research. 2007, 67 (21): 10484-10490. 10.1158/0008-5472.CAN-07-2607.CrossRefPubMedPubMedCentral
20.
go back to reference Seligson DB, Horvath S, McBrian MA, Mah V, Yu H, Tze S, Wang Q, Chia D, Goodglick L, Kurdistani SK: Global levels of histone modifications predict prognosis in different cancers. Am J Pathol. 2009, 174 (5): 1619-1628. 10.2353/ajpath.2009.080874.CrossRefPubMedPubMedCentral Seligson DB, Horvath S, McBrian MA, Mah V, Yu H, Tze S, Wang Q, Chia D, Goodglick L, Kurdistani SK: Global levels of histone modifications predict prognosis in different cancers. Am J Pathol. 2009, 174 (5): 1619-1628. 10.2353/ajpath.2009.080874.CrossRefPubMedPubMedCentral
21.
go back to reference Jazirehi AR, Ng CP, Gan XH, Schiller G, Bonavida B: Adriamycin sensitizes the adriamycin-resistant 8226/Dox40 human multiple myeloma cells to Apo2L/tumor necrosis factor-related apoptosis-inducing ligand-mediated (TRAIL) apoptosis. Clin Cancer Res. 2001, 7 (12): 3874-3883.PubMed Jazirehi AR, Ng CP, Gan XH, Schiller G, Bonavida B: Adriamycin sensitizes the adriamycin-resistant 8226/Dox40 human multiple myeloma cells to Apo2L/tumor necrosis factor-related apoptosis-inducing ligand-mediated (TRAIL) apoptosis. Clin Cancer Res. 2001, 7 (12): 3874-3883.PubMed
22.
go back to reference Zaravinos A, Kanellou P, Baritaki S, Bonavida B, Spandidos DA: BRAF and RKIP are significantly decreased in cutaneous squamous cell carcinoma. Cell cycle Georgetown, Tex. 2009, 8 (9): 1402-1408. 10.4161/cc.8.9.8308.CrossRefPubMed Zaravinos A, Kanellou P, Baritaki S, Bonavida B, Spandidos DA: BRAF and RKIP are significantly decreased in cutaneous squamous cell carcinoma. Cell cycle Georgetown, Tex. 2009, 8 (9): 1402-1408. 10.4161/cc.8.9.8308.CrossRefPubMed
23.
go back to reference Keller ET, Fu Z, Yeung K, Brennan M: Raf kinase inhibitor protein: a prostate cancer metastasis suppressor gene. Cancer letters. 2004, 207 (2): 131-137. 10.1016/j.canlet.2004.02.006.CrossRefPubMed Keller ET, Fu Z, Yeung K, Brennan M: Raf kinase inhibitor protein: a prostate cancer metastasis suppressor gene. Cancer letters. 2004, 207 (2): 131-137. 10.1016/j.canlet.2004.02.006.CrossRefPubMed
24.
go back to reference Lee HC, Tian B, Sedivy JM, Wands JR, Kim M: Loss of Raf kinase inhibitor protein promotes cell proliferation and migration of human hepatoma cells. Gastroenterology. 2006, 131 (4): 1208-1217. 10.1053/j.gastro.2006.07.012.CrossRefPubMedPubMedCentral Lee HC, Tian B, Sedivy JM, Wands JR, Kim M: Loss of Raf kinase inhibitor protein promotes cell proliferation and migration of human hepatoma cells. Gastroenterology. 2006, 131 (4): 1208-1217. 10.1053/j.gastro.2006.07.012.CrossRefPubMedPubMedCentral
25.
go back to reference Zlobec I, Baker K, Minoo P, Jass JR, Terracciano L, Lugli A: Node-negative colorectal cancer at high risk of distant metastasis identified by combined analysis of lymph node status, vascular invasion, and Raf-1 kinase inhibitor protein expression. Clin Cancer Res. 2008, 14 (1): 143-148. 10.1158/1078-0432.CCR-07-1380.CrossRefPubMed Zlobec I, Baker K, Minoo P, Jass JR, Terracciano L, Lugli A: Node-negative colorectal cancer at high risk of distant metastasis identified by combined analysis of lymph node status, vascular invasion, and Raf-1 kinase inhibitor protein expression. Clin Cancer Res. 2008, 14 (1): 143-148. 10.1158/1078-0432.CCR-07-1380.CrossRefPubMed
26.
go back to reference Li HZ, Wang Y, Gao Y, Shao J, Zhao XL, Deng WM, Liu YX, Yang J, Yao Z: Effects of raf kinase inhibitor protein expression on metastasis and progression of human epithelial ovarian cancer. Mol Cancer Res. 2008, 6 (6): 917-928. 10.1158/1541-7786.MCR-08-0093.CrossRefPubMed Li HZ, Wang Y, Gao Y, Shao J, Zhao XL, Deng WM, Liu YX, Yang J, Yao Z: Effects of raf kinase inhibitor protein expression on metastasis and progression of human epithelial ovarian cancer. Mol Cancer Res. 2008, 6 (6): 917-928. 10.1158/1541-7786.MCR-08-0093.CrossRefPubMed
27.
go back to reference Rath O, Park S, Tang HH, Banfield MJ, Brady RL, Lee YC, Dignam JD, Sedivy JM, Kolch W, Yeung KC: The RKIP (Raf-1 Kinase Inhibitor Protein) conserved pocket binds to the phosphorylated N-region of Raf-1 and inhibits the Raf-1-mediated activated phosphorylation of MEK. Cellular signalling. 2008, 20 (5): 935-941. 10.1016/j.cellsig.2008.01.012.CrossRefPubMed Rath O, Park S, Tang HH, Banfield MJ, Brady RL, Lee YC, Dignam JD, Sedivy JM, Kolch W, Yeung KC: The RKIP (Raf-1 Kinase Inhibitor Protein) conserved pocket binds to the phosphorylated N-region of Raf-1 and inhibits the Raf-1-mediated activated phosphorylation of MEK. Cellular signalling. 2008, 20 (5): 935-941. 10.1016/j.cellsig.2008.01.012.CrossRefPubMed
28.
go back to reference Huang J, Mahavadi S, Sriwai W, Grider JR, Murthy KS: Cross-regulation of VPAC(2) receptor desensitization by M(3) receptors via PKC-mediated phosphorylation of RKIP and inhibition of GRK2. American journal of physiology. 2007, 292 (3): G867-874.PubMed Huang J, Mahavadi S, Sriwai W, Grider JR, Murthy KS: Cross-regulation of VPAC(2) receptor desensitization by M(3) receptors via PKC-mediated phosphorylation of RKIP and inhibition of GRK2. American journal of physiology. 2007, 292 (3): G867-874.PubMed
29.
go back to reference Granovsky AE, Clark MC, McElheny D, Heil G, Hong J, Liu X, Kim Y, Joachimiak G, Joachimiak A, Koide S, Rosner MR: Raf kinase inhibitory protein function is regulated via a flexible pocket and novel phosphorylation-dependent mechanism. Molecular and cellular biology. 2009, 29 (5): 1306-1320. 10.1128/MCB.01271-08.CrossRefPubMed Granovsky AE, Clark MC, McElheny D, Heil G, Hong J, Liu X, Kim Y, Joachimiak G, Joachimiak A, Koide S, Rosner MR: Raf kinase inhibitory protein function is regulated via a flexible pocket and novel phosphorylation-dependent mechanism. Molecular and cellular biology. 2009, 29 (5): 1306-1320. 10.1128/MCB.01271-08.CrossRefPubMed
30.
go back to reference Jazirehi AR, Huerta-Yepez S, Cheng G, Bonavida B: Rituximab (chimeric anti-CD20 monoclonal antibody) inhibits the constitutive nuclear factor-{kappa}B signaling pathway in non-Hodgkin's lymphoma B-cell lines: role in sensitization to chemotherapeutic drug-induced apoptosis. Cancer research. 2005, 65 (1): 264-276.PubMed Jazirehi AR, Huerta-Yepez S, Cheng G, Bonavida B: Rituximab (chimeric anti-CD20 monoclonal antibody) inhibits the constitutive nuclear factor-{kappa}B signaling pathway in non-Hodgkin's lymphoma B-cell lines: role in sensitization to chemotherapeutic drug-induced apoptosis. Cancer research. 2005, 65 (1): 264-276.PubMed
31.
go back to reference Jazirehi AR, Vega MI, Chatterjee D, Goodglick L, Bonavida B: Inhibition of the Raf-MEK1/2-ERK1/2 signaling pathway, Bcl-xL down-regulation, and chemosensitization of non-Hodgkin's lymphoma B cells by Rituximab. Cancer research. 2004, 64 (19): 7117-7126. 10.1158/0008-5472.CAN-03-3500.CrossRefPubMed Jazirehi AR, Vega MI, Chatterjee D, Goodglick L, Bonavida B: Inhibition of the Raf-MEK1/2-ERK1/2 signaling pathway, Bcl-xL down-regulation, and chemosensitization of non-Hodgkin's lymphoma B cells by Rituximab. Cancer research. 2004, 64 (19): 7117-7126. 10.1158/0008-5472.CAN-03-3500.CrossRefPubMed
32.
go back to reference Baritaki S, Chapman A, Yeung K, Spandidos DA, Palladino M, Bonavida B: 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. 2009 Baritaki S, Chapman A, Yeung K, Spandidos DA, Palladino M, Bonavida B: 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. 2009
33.
go back to reference Eves EM, Shapiro P, Naik K, Klein UR, Trakul N, Rosner MR: Raf kinase inhibitory protein regulates aurora B kinase and the spindle checkpoint. Molecular cell. 2006, 23 (4): 561-574. 10.1016/j.molcel.2006.07.015.CrossRefPubMedPubMedCentral Eves EM, Shapiro P, Naik K, Klein UR, Trakul N, Rosner MR: Raf kinase inhibitory protein regulates aurora B kinase and the spindle checkpoint. Molecular cell. 2006, 23 (4): 561-574. 10.1016/j.molcel.2006.07.015.CrossRefPubMedPubMedCentral
34.
go back to reference Zhu J, Woods D, McMahon M, Bishop JM: Senescence of human fibroblasts induced by oncogenic Raf. Genes & development. 1998, 12 (19): 2997-3007. 10.1101/gad.12.19.2997.CrossRef Zhu J, Woods D, McMahon M, Bishop JM: Senescence of human fibroblasts induced by oncogenic Raf. Genes & development. 1998, 12 (19): 2997-3007. 10.1101/gad.12.19.2997.CrossRef
35.
go back to reference Woods D, Parry D, Cherwinski H, Bosch E, Lees E, McMahon M: Raf-induced proliferation or cell cycle arrest is determined by the level of Raf activity with arrest mediated by p21Cip1. Molecular and cellular biology. 1997, 17 (9): 5598-5611.CrossRefPubMedPubMedCentral Woods D, Parry D, Cherwinski H, Bosch E, Lees E, McMahon M: Raf-induced proliferation or cell cycle arrest is determined by the level of Raf activity with arrest mediated by p21Cip1. Molecular and cellular biology. 1997, 17 (9): 5598-5611.CrossRefPubMedPubMedCentral
36.
go back to reference Houben R, Vetter-Kauczok CS, Ortmann S, Rapp UR, Broecker EB, Becker JC: Phospho-ERK staining is a poor indicator of the mutational status of BRAF and NRAS in human melanoma. The Journal of investigative dermatology. 2008, 128 (8): 2003-2012. 10.1038/jid.2008.30.CrossRefPubMed Houben R, Vetter-Kauczok CS, Ortmann S, Rapp UR, Broecker EB, Becker JC: Phospho-ERK staining is a poor indicator of the mutational status of BRAF and NRAS in human melanoma. The Journal of investigative dermatology. 2008, 128 (8): 2003-2012. 10.1038/jid.2008.30.CrossRefPubMed
Metadata
Title
Expression of phosphorylated raf kinase inhibitor protein (pRKIP) is a predictor of lung cancer survival
Authors
Sara Huerta-Yepez
Nam K Yoon
Angeles Hernandez-Cueto
Vei Mah
Clara M Rivera-Pazos
Devasis Chatterjee
Mario I Vega
Erin L Maresh
Steve Horvath
David Chia
Benjamin Bonavida
Lee Goodglick
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2011
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-11-259

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