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Erschienen in: Pathology & Oncology Research 2/2012

01.04.2012 | Research

Down-Regulated Expression of HSP70 in Correlation with Clinicopathology of Cholangiocarcinoma

verfasst von: Sirintip Boonjaraspinyo, Thidarut Boonmars, Sasithorn Kaewkes, Porntip Laummaunwai, Somchai Pinlaor, Watchalin Loilome, Puangrat Yongvanit, Zhiliang Wu, Anucha Puapairoj, Vajarabhongsa Bhudhisawasdi

Erschienen in: Pathology & Oncology Research | Ausgabe 2/2012

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Abstract

Cholangiocarcinoma is a crucial health problem in northeast Thailand. Although rare, it is a highly fatal disease and the prognosis of CCA patients is very poor. To determine if expression of specific genes is useful for diagnosis and prognosis for CCA. We examined the expression of HSP70, HSP90, RB1, cyclin D1, and HDAC6 in 50 resections of human CCA tissues by quantitative real-time PCR. The expression of HSP70, RB1, and HDAC6 was “dominant down-regulation,” while the expression of cyclin D1 and HSP90 was “dominant up-regulation.” There were no correlations between RB1, cyclin D1, HSP90, and clinicopathological parameters such as status, histology type, histological grading, stage of CCA, and metastasis. A significant association was found between HDAC6 and CCA staging (p = 0.000), CCA gross type and HSP70 (p = 0.046) as well as RB1 expression (p = 0.046). Patients with down-regulation of HSP70 had significantly poorer prognosis than those in the up-regulation group (p = 0.002). Expression of HSP70 may be useful as a new prognostic marker for CCA.
Literatur
1.
Zurück zum Zitat International Agency for Research on Cancer (IARC) (1994) Infection with liver flukes (Opisthorchis viverrini, Opisthorchis felineus and Clonorchis sinensis). IARC Monogr Eval Carcinog Risks Hum 61:121–175 International Agency for Research on Cancer (IARC) (1994) Infection with liver flukes (Opisthorchis viverrini, Opisthorchis felineus and Clonorchis sinensis). IARC Monogr Eval Carcinog Risks Hum 61:121–175
2.
Zurück zum Zitat Sithithaworn P, Haswell-Elkins MR (2003) Epidemiology of Opisthorchis viverrini. Acta Trop 88:187–194PubMedCrossRef Sithithaworn P, Haswell-Elkins MR (2003) Epidemiology of Opisthorchis viverrini. Acta Trop 88:187–194PubMedCrossRef
3.
Zurück zum Zitat Sripa B, Pairojkul C (2008) Cholangiocarcinoma: lessons from Thailand. Curr Opin Gastroenterol 24:349–156PubMedCrossRef Sripa B, Pairojkul C (2008) Cholangiocarcinoma: lessons from Thailand. Curr Opin Gastroenterol 24:349–156PubMedCrossRef
4.
Zurück zum Zitat Freeman BC, Yamamoto KR (2002) Disassembly of transcriptional regulatory complexes by molecular chaperones. Science 296:2232–2235PubMedCrossRef Freeman BC, Yamamoto KR (2002) Disassembly of transcriptional regulatory complexes by molecular chaperones. Science 296:2232–2235PubMedCrossRef
5.
Zurück zum Zitat Beere HM, Wolf BB, Cain K et al (2000) Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome. Nat Cell Biol 2:469–475PubMedCrossRef Beere HM, Wolf BB, Cain K et al (2000) Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome. Nat Cell Biol 2:469–475PubMedCrossRef
6.
Zurück zum Zitat Madhavan J, Ganesh A, Kumaramanickavel G (2008) Retinoblastoma: from disease to discovery. Ophthalmic Res 40:221–226PubMedCrossRef Madhavan J, Ganesh A, Kumaramanickavel G (2008) Retinoblastoma: from disease to discovery. Ophthalmic Res 40:221–226PubMedCrossRef
7.
Zurück zum Zitat Das SK, Hashimoto T, Shimizu K et al (2005) Fucoxanthin induces cell cycle arrest at G0/G1 phase in human colon carcinoma cells through up-regulation of p21WAF1/Cip1 2. Biochim Biophys Acta 1726:328–335PubMedCrossRef Das SK, Hashimoto T, Shimizu K et al (2005) Fucoxanthin induces cell cycle arrest at G0/G1 phase in human colon carcinoma cells through up-regulation of p21WAF1/Cip1 2. Biochim Biophys Acta 1726:328–335PubMedCrossRef
8.
Zurück zum Zitat Lundberg AS, Weinberg RA (1998) Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-cdk complexes. Mol Cell Biol 18:753–761PubMed Lundberg AS, Weinberg RA (1998) Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-cdk complexes. Mol Cell Biol 18:753–761PubMed
10.
Zurück zum Zitat Hideshima T, Bradner JE, Wong J et al (2005) Small-molecule inhibition of proteasome and aggresome function induces synergistic antitumor activity in multiple myeloma. Proc Natl Acad Sci U S A 102:8567–8572PubMedCrossRef Hideshima T, Bradner JE, Wong J et al (2005) Small-molecule inhibition of proteasome and aggresome function induces synergistic antitumor activity in multiple myeloma. Proc Natl Acad Sci U S A 102:8567–8572PubMedCrossRef
11.
Zurück zum Zitat DeOliveira ML, Cunningham SC, Cameron JL et al (2007) Cholangiocarcinoma: thirty-one-year experience with 564 patients at a single institution. Ann Surg 245:755–762PubMedCrossRef DeOliveira ML, Cunningham SC, Cameron JL et al (2007) Cholangiocarcinoma: thirty-one-year experience with 564 patients at a single institution. Ann Surg 245:755–762PubMedCrossRef
12.
Zurück zum Zitat Kondo S, Takada T, Miyazaki M et al (2008) Guidelines for the management of biliary tract and ampullary carcinomas: surgical treatment. J Hepatobiliary Pancreat Surg 15:41–54PubMedCrossRef Kondo S, Takada T, Miyazaki M et al (2008) Guidelines for the management of biliary tract and ampullary carcinomas: surgical treatment. J Hepatobiliary Pancreat Surg 15:41–54PubMedCrossRef
13.
Zurück zum Zitat Uttaravichien T, Bhudhisawasdi V, Pairojkul C et al (1999) Intrahepatic cholangiocarcinoma in Thailand. J Hepatobiliary Pancreat Surg 62:128–135CrossRef Uttaravichien T, Bhudhisawasdi V, Pairojkul C et al (1999) Intrahepatic cholangiocarcinoma in Thailand. J Hepatobiliary Pancreat Surg 62:128–135CrossRef
14.
Zurück zum Zitat Green A, Uttaravichien T, Bhudhisawasdi V et al (1991) Cholangiocarcinoma in north east Thailand: a hospital-based study. Trop Geogr Med 43:193–198PubMed Green A, Uttaravichien T, Bhudhisawasdi V et al (1991) Cholangiocarcinoma in north east Thailand: a hospital-based study. Trop Geogr Med 43:193–198PubMed
15.
Zurück zum Zitat Boonmars T, Wu Z, Boonjaruspinyo S et al (2009) Alterations of gene expression of RB pathway in Opisthorchis viverrini infection-induced cholangiocarcinoma. Parasitol Res 105:1273–1281PubMedCrossRef Boonmars T, Wu Z, Boonjaruspinyo S et al (2009) Alterations of gene expression of RB pathway in Opisthorchis viverrini infection-induced cholangiocarcinoma. Parasitol Res 105:1273–1281PubMedCrossRef
16.
Zurück zum Zitat Liver Cancer Study Group of Japan (2003) The general rules for the clinical and pathological study of primary liver cancer, 2th ed. Tokyo: Kanehara 15 Liver Cancer Study Group of Japan (2003) The general rules for the clinical and pathological study of primary liver cancer, 2th ed. Tokyo: Kanehara 15
17.
Zurück zum Zitat Nakanuma Y, Sripa B, Batanasapt V et al (2000) Intrahepatic cholangiocarcinoma. In: Hamilton SR, Aaltonen LA (eds) World Health Organization classification of tumours: pathology and genetics––tumours of the digestive system. IARC Press, Lyon, pp 173–180 Nakanuma Y, Sripa B, Batanasapt V et al (2000) Intrahepatic cholangiocarcinoma. In: Hamilton SR, Aaltonen LA (eds) World Health Organization classification of tumours: pathology and genetics––tumours of the digestive system. IARC Press, Lyon, pp 173–180
18.
Zurück zum Zitat Edge SB, Byrd DR, Compton CC et al (2009) AJCC cancer staging manual, 7th edn. Springer-Verlag Press, New York Edge SB, Byrd DR, Compton CC et al (2009) AJCC cancer staging manual, 7th edn. Springer-Verlag Press, New York
19.
Zurück zum Zitat Ciocca DR, Calderwood SK (2005) Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones 10:86–103PubMedCrossRef Ciocca DR, Calderwood SK (2005) Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones 10:86–103PubMedCrossRef
20.
Zurück zum Zitat Chuma M, Sakamoto M, Yamazaki K et al (2003) Expression profiling in multistage hepatocarcinogenesis: identification of HSP70 as a molecular marker of early hepatocellular carcinoma. Hepatology 37:198–207PubMedCrossRef Chuma M, Sakamoto M, Yamazaki K et al (2003) Expression profiling in multistage hepatocarcinogenesis: identification of HSP70 as a molecular marker of early hepatocellular carcinoma. Hepatology 37:198–207PubMedCrossRef
21.
Zurück zum Zitat Lazaris AC, Chatzigianni EB, Panoussopoulos D et al (1997) Proliferating cell nuclear antigen and heat shock protein 70 immunolocalization in invasive ductal breast cancer not otherwise specified. Breast Cancer Res Treat 43:43–51PubMedCrossRef Lazaris AC, Chatzigianni EB, Panoussopoulos D et al (1997) Proliferating cell nuclear antigen and heat shock protein 70 immunolocalization in invasive ductal breast cancer not otherwise specified. Breast Cancer Res Treat 43:43–51PubMedCrossRef
22.
Zurück zum Zitat Nanbu K, Konishi I, Komatsu T et al (1996) Expression of heat shock proteins HSP70 and HSP90 in endometrial carcinomas. Correlation with clinicopathology, sex steroid receptor status, and p53 protein expression. Cancer 77:330–338PubMedCrossRef Nanbu K, Konishi I, Komatsu T et al (1996) Expression of heat shock proteins HSP70 and HSP90 in endometrial carcinomas. Correlation with clinicopathology, sex steroid receptor status, and p53 protein expression. Cancer 77:330–338PubMedCrossRef
23.
Zurück zum Zitat Abd el All H, Rey A, Duvillard P (1998) Expression of heat shock protein 70 and c-myc in cervical carcinoma. Anticancer Res 18:1533–1536PubMed Abd el All H, Rey A, Duvillard P (1998) Expression of heat shock protein 70 and c-myc in cervical carcinoma. Anticancer Res 18:1533–1536PubMed
24.
Zurück zum Zitat Aghdassi A, Phillips P, Dudeja V et al (2007) Heat shock protein 70 increases tumorigenicity and inhibits apoptosis in pancreatic adenocarcinoma. Cancer Res 67:616–625PubMedCrossRef Aghdassi A, Phillips P, Dudeja V et al (2007) Heat shock protein 70 increases tumorigenicity and inhibits apoptosis in pancreatic adenocarcinoma. Cancer Res 67:616–625PubMedCrossRef
25.
Zurück zum Zitat Basso AD, Solit DB, Chiosis G et al (2002) Akt forms an intracellular complex with heat shock protein 90 (Hsp90) and Cdc37 and is destabilized by inhibitors of Hsp90 function. J Biol Chem 277:39858–39866PubMedCrossRef Basso AD, Solit DB, Chiosis G et al (2002) Akt forms an intracellular complex with heat shock protein 90 (Hsp90) and Cdc37 and is destabilized by inhibitors of Hsp90 function. J Biol Chem 277:39858–39866PubMedCrossRef
26.
Zurück zum Zitat Vanden Berghe T, Kalai M, van Loo G et al (2003) Disruption of HSP90 function reverts tumor necrosis factor-induced necrosis to apoptosis. J Biol Chem 278:5622–5629PubMedCrossRef Vanden Berghe T, Kalai M, van Loo G et al (2003) Disruption of HSP90 function reverts tumor necrosis factor-induced necrosis to apoptosis. J Biol Chem 278:5622–5629PubMedCrossRef
27.
Zurück zum Zitat Chen G, Cao P, Goeddel DV (2002) TNF-induced recruitment and activation of the IKK complex require Cdc37 and Hsp90. Mol Cell 9:401–410PubMedCrossRef Chen G, Cao P, Goeddel DV (2002) TNF-induced recruitment and activation of the IKK complex require Cdc37 and Hsp90. Mol Cell 9:401–410PubMedCrossRef
28.
Zurück zum Zitat Jameel A, Skilton RA, Campbell TA et al (1992) Clinical and biological significance of HSP89 alpha in human breast cancer. Int J Cancer 50:409–415PubMedCrossRef Jameel A, Skilton RA, Campbell TA et al (1992) Clinical and biological significance of HSP89 alpha in human breast cancer. Int J Cancer 50:409–415PubMedCrossRef
29.
Zurück zum Zitat Yano M, Naito Z, Yokoyama M et al (1999) Expression of Hsp90 and cyclin D1 in human breast cancer. Cancer Lett 137:45–51PubMedCrossRef Yano M, Naito Z, Yokoyama M et al (1999) Expression of Hsp90 and cyclin D1 in human breast cancer. Cancer Lett 137:45–51PubMedCrossRef
30.
Zurück zum Zitat Liu X, Ye L, Wang J et al (1999) Expression of heat shock protein 90 beta in human gastric cancer tissue and SGD7901/VCR of MDR-type gastric cancer cell line. Chin Med J (Engl) 112:1133–1137 Liu X, Ye L, Wang J et al (1999) Expression of heat shock protein 90 beta in human gastric cancer tissue and SGD7901/VCR of MDR-type gastric cancer cell line. Chin Med J (Engl) 112:1133–1137
31.
Zurück zum Zitat Ogata M, Naito Z, Tanaka S et al (2000) Overexpression and localization of heat shock proteins mRNA in pancreatic carcinoma. J Nippon Med Sch 67:177–185CrossRef Ogata M, Naito Z, Tanaka S et al (2000) Overexpression and localization of heat shock proteins mRNA in pancreatic carcinoma. J Nippon Med Sch 67:177–185CrossRef
32.
Zurück zum Zitat Cardillo MR, Sale P, Di Silverio F (2000) Heat shock protein-90, IL-6 and IL-10 in bladder cancer. Anticancer Res 20:4579–4583PubMed Cardillo MR, Sale P, Di Silverio F (2000) Heat shock protein-90, IL-6 and IL-10 in bladder cancer. Anticancer Res 20:4579–4583PubMed
33.
Zurück zum Zitat Bosco EE, Wang Y, Xu H et al (2007) The retinoblastoma tumor suppressor modifies the therapeutic response of breast cancer. J Clin Invest 117:218–228PubMedCrossRef Bosco EE, Wang Y, Xu H et al (2007) The retinoblastoma tumor suppressor modifies the therapeutic response of breast cancer. J Clin Invest 117:218–228PubMedCrossRef
34.
Zurück zum Zitat Contu SS, Contu PC, Damin DC et al (2007) pRB expression in esophageal mucosa of individuals at high risk for squamous cell carcinoma of the esophagus. World J Gastroenterol 13:1728–1731PubMed Contu SS, Contu PC, Damin DC et al (2007) pRB expression in esophageal mucosa of individuals at high risk for squamous cell carcinoma of the esophagus. World J Gastroenterol 13:1728–1731PubMed
35.
Zurück zum Zitat Chim CS, Wong KY, Loong F et al (2007) Frequent epigenetic inactivation of Rb1 in addition to p15 and p16 in mantle cell and follicular lymphoma. Hum Pathol 38:1849–1857PubMedCrossRef Chim CS, Wong KY, Loong F et al (2007) Frequent epigenetic inactivation of Rb1 in addition to p15 and p16 in mantle cell and follicular lymphoma. Hum Pathol 38:1849–1857PubMedCrossRef
36.
Zurück zum Zitat Chatterjee SJ, Datar R, Youssefzadeh D et al (2004) Combined effects of p53, p21, and pRb expression in the progression of bladder transitional cell carcinoma. J Clin Oncol 22:1007–1103PubMedCrossRef Chatterjee SJ, Datar R, Youssefzadeh D et al (2004) Combined effects of p53, p21, and pRb expression in the progression of bladder transitional cell carcinoma. J Clin Oncol 22:1007–1103PubMedCrossRef
37.
Zurück zum Zitat Sgambato A, Migaldi M, Faraglia B et al (2002) Cyclin D1 expression in papillary superficial bladder cancer: its association with other cell cycle-associated proteins, cell proliferation and clinical outcome. Int J Cancer 97:671–678PubMedCrossRef Sgambato A, Migaldi M, Faraglia B et al (2002) Cyclin D1 expression in papillary superficial bladder cancer: its association with other cell cycle-associated proteins, cell proliferation and clinical outcome. Int J Cancer 97:671–678PubMedCrossRef
38.
Zurück zum Zitat Deeb KK, Michalowska AM, Yoon CY et al (2007) Identification of an integrated SV40 T/t-antigen cancer signature in aggressive human breast, prostate, and lung carcinomas with poor prognosis. Cancer Res 67:8065–8080PubMedCrossRef Deeb KK, Michalowska AM, Yoon CY et al (2007) Identification of an integrated SV40 T/t-antigen cancer signature in aggressive human breast, prostate, and lung carcinomas with poor prognosis. Cancer Res 67:8065–8080PubMedCrossRef
39.
Zurück zum Zitat Kang YK, Kim WH, Jang JJ (2002) Expression of G1-S modulators (p53, p16, p27, cyclin D1, Rb) and Smad4/Dpc4 in intrahepatic cholangiocarcinoma. Hum Pathol 33:877–888PubMedCrossRef Kang YK, Kim WH, Jang JJ (2002) Expression of G1-S modulators (p53, p16, p27, cyclin D1, Rb) and Smad4/Dpc4 in intrahepatic cholangiocarcinoma. Hum Pathol 33:877–888PubMedCrossRef
40.
Zurück zum Zitat Sumrejkanchanakij P, Tamamori-Adachi M, Matsunaga Y et al (2003) Role of cyclin D1 cytoplasmic sequestration in the survival of postmitotic neurons. Oncogene 22:8723–8730PubMedCrossRef Sumrejkanchanakij P, Tamamori-Adachi M, Matsunaga Y et al (2003) Role of cyclin D1 cytoplasmic sequestration in the survival of postmitotic neurons. Oncogene 22:8723–8730PubMedCrossRef
41.
Zurück zum Zitat Kella VK, Constantine R, Parikh NS et al (2009) Mantle cell lymphoma of the gastrointestinal tract presenting with multiple intussusceptions – case report and review of literature. World J Surg Oncol 7:60PubMedCrossRef Kella VK, Constantine R, Parikh NS et al (2009) Mantle cell lymphoma of the gastrointestinal tract presenting with multiple intussusceptions – case report and review of literature. World J Surg Oncol 7:60PubMedCrossRef
42.
Zurück zum Zitat Gillett C, Smith P, Gregory W et al (1996) Cyclin D1 and prognosis in human breast cancer. Int J Cancer 69:92–99PubMedCrossRef Gillett C, Smith P, Gregory W et al (1996) Cyclin D1 and prognosis in human breast cancer. Int J Cancer 69:92–99PubMedCrossRef
43.
Zurück zum Zitat Azechi H, Nishida N, Fukuda Y et al (2001) Disruption of the p16/cyclin D1/retinoblastoma protein pathway in the majority of human hepatocellular carcinomas. Oncology 60:346–354PubMedCrossRef Azechi H, Nishida N, Fukuda Y et al (2001) Disruption of the p16/cyclin D1/retinoblastoma protein pathway in the majority of human hepatocellular carcinomas. Oncology 60:346–354PubMedCrossRef
44.
Zurück zum Zitat Mitra AP, Datar RH, Cote RJ (2006) Molecular pathways in invasive bladder cancer: new insights into mechanisms, progression, and target identification. J Clin Oncol 24:5552–5564PubMedCrossRef Mitra AP, Datar RH, Cote RJ (2006) Molecular pathways in invasive bladder cancer: new insights into mechanisms, progression, and target identification. J Clin Oncol 24:5552–5564PubMedCrossRef
45.
Zurück zum Zitat Garcea G, Neal CP, Pattenden CJ et al (2005) Molecular prognostic markers in pancreatic cancer: a systematic review. Eur J Cancer 41:2213–2236PubMedCrossRef Garcea G, Neal CP, Pattenden CJ et al (2005) Molecular prognostic markers in pancreatic cancer: a systematic review. Eur J Cancer 41:2213–2236PubMedCrossRef
46.
Zurück zum Zitat Zhang Z, Yamashita H, Toyama T et al (2004) HDAC6 expression is correlated with better survival in breast cancer. Clin Cancer Res 10:6962–6968PubMedCrossRef Zhang Z, Yamashita H, Toyama T et al (2004) HDAC6 expression is correlated with better survival in breast cancer. Clin Cancer Res 10:6962–6968PubMedCrossRef
Metadaten
Titel
Down-Regulated Expression of HSP70 in Correlation with Clinicopathology of Cholangiocarcinoma
verfasst von
Sirintip Boonjaraspinyo
Thidarut Boonmars
Sasithorn Kaewkes
Porntip Laummaunwai
Somchai Pinlaor
Watchalin Loilome
Puangrat Yongvanit
Zhiliang Wu
Anucha Puapairoj
Vajarabhongsa Bhudhisawasdi
Publikationsdatum
01.04.2012
Verlag
Springer Netherlands
Erschienen in
Pathology & Oncology Research / Ausgabe 2/2012
Print ISSN: 1219-4956
Elektronische ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-011-9432-5

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