title: Decreased expression of heat shock protein 20 in colorectal cancer and its implication in tumorigenesis.
abstract: Heat shock protein 20 (HSP20), which is a member of the small heat shock protein family, is known to participate in many pathological processes, such as asthma, intimal hyperplasia, and insulin resistance. However, the function of HSP20 in cancer development is not yet fully understood. In this study, we identified HSP20 as a down-regulated protein in 20 resected colorectal cancer (CRC) specimens compared with their paired normal tissues. Because HSP20 proteins were barely detectable in HCT-116 cells (a human colorectal cancer cell line), recombinant adenovirus encoding HSP20 (Ad-HSP20) was used to induce HSP20 overexpression in HCT-116 cells. Infection of Ad-HSP20, but not control adenovirus (Ad-GFP), reduced viability, and induced massive apoptosis in a time-dependent manner. The forced expression of HSP20 enhanced caspase-3/7 activity and down-regulated the anti-apoptotic Bcl-xL and Bcl-2 mRNA and protein levels. In addition, immunohistochemical analysis of 94 CRC specimens for HSP20 protein showed that reduced HSP20 expression was related to advanced TNM stage, lymph node metastasis, and tumor recurrence. Our study shows, for the first time, that expression of the HSP20 protein has a pro-death role in colorectal cancer cells. Therefore, HSP20 may have value as a prognostic tumor marker and its overexpression might be a novel strategy for CRC therapy.
authors.affiliation: Department of Surgery, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Republic of Korea.
authors.forename: Young-Tae
authors.initials: YT
authors.lastname: Ju
authors.forename: Seung-Jin
authors.initials: SJ
authors.lastname: Kwag
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Park
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Jung
authors.forename: Chi-Young
authors.initials: CY
authors.lastname: Jeong
authors.forename: Sang-Ho
authors.initials: SH
authors.lastname: Jeong
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Lee
authors.forename: Sang-Kyung
authors.initials: SK
authors.lastname: Choi
authors.forename: Kee Ryeon
authors.initials: KR
authors.lastname: Kang
authors.forename: Young-Sool
authors.initials: YS
authors.lastname: Hah
authors.forename: Soon-Chan
authors.initials: SC
authors.lastname: Hong
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D063646:Carcinogenesis / Q000235:genetics* / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002470:Cell Survival / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors / Q000235:genetics; D045325:HCT116 Cells; D050886:HSP20 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494811:BCL2L1 protein, human; D050886:HSP20 Heat-Shock Proteins; C494382:HSPB6 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D053148:Caspase 3; D053179:Caspase 7
keywords: APOPTOSIS; COLORECTAL CANCER; HEAT-SHOCK PROTEIN 20; TUMOR MARKER