Top

Published in:

01-04-2012 | Research

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

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

Published in: Pathology & Oncology Research | Issue 2/2012

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.

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

Sithithaworn P, Haswell-Elkins MR (2003) Epidemiology of Opisthorchis viverrini. Acta Trop 88:187–194PubMedCrossRef

Sripa B, Pairojkul C (2008) Cholangiocarcinoma: lessons from Thailand. Curr Opin Gastroenterol 24:349–156PubMedCrossRef

Freeman BC, Yamamoto KR (2002) Disassembly of transcriptional regulatory complexes by molecular chaperones. Science 296:2232–2235PubMedCrossRef

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

Madhavan J, Ganesh A, Kumaramanickavel G (2008) Retinoblastoma: from disease to discovery. Ophthalmic Res 40:221–226PubMedCrossRef

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

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

Glozak MA, Seto E (2007) Histone deacetylases and cancer. Oncogene 26:5420–5432PubMedCrossRef

10.

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.

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.

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.

Uttaravichien T, Bhudhisawasdi V, Pairojkul C et al (1999) Intrahepatic cholangiocarcinoma in Thailand. J Hepatobiliary Pancreat Surg 62:128–135CrossRef

14.

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.

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.

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.

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.

Edge SB, Byrd DR, Compton CC et al (2009) AJCC cancer staging manual, 7th edn. Springer-Verlag Press, New York

19.

Ciocca DR, Calderwood SK (2005) Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones 10:86–103PubMedCrossRef

20.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Gillett C, Smith P, Gregory W et al (1996) Cyclin D1 and prognosis in human breast cancer. Int J Cancer 69:92–99PubMedCrossRef

43.

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.

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.

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.

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

Title: Down-Regulated Expression of HSP70 in Correlation with Clinicopathology of Cholangiocarcinoma
Authors: Sirintip Boonjaraspinyo
Thidarut Boonmars
Sasithorn Kaewkes
Porntip Laummaunwai
Somchai Pinlaor
Watchalin Loilome
Puangrat Yongvanit
Zhiliang Wu
Anucha Puapairoj
Vajarabhongsa Bhudhisawasdi
Publication date: 01-04-2012
Publisher: Springer Netherlands
Published in: Pathology & Oncology Research / Issue 2/2012
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI: https://doi.org/10.1007/s12253-011-9432-5

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2012

Periacinar Retraction Clefting in Nonneoplastic and Neoplastic Prostatic Glands: Artifact or Molecular Involvement

p53 Binds to Estrogen Receptor 1 Promoter in Human Breast Cancer Cells

Prognostic Value of Matrix Metalloproteinase-1/ Proteinase-Activated Receptor-1 Signaling Axis in Hepatocellular Carcinoma

Effect of shRNA Mediated Down-Regulation of Annexin A2 on Biological Behavior of Human Lung Adencarcinoma Cells A549

Two Cases of Low-Grade Endometriod Carcinoma Associated with Undifferentiated Carcinoma of the Uterus (Dedifferentiated Carcinoma): A Molecular Study

ABCC2 (MRP2, cMOAT) Localized in the Nuclear Envelope of Breast Carcinoma Cells Correlates with Poor Clinical Outcome

Keynote webinar | Spotlight on antibody–drug conjugates in cancer