title: Differential expression of heat shock protein 90 isoforms in small cell lung cancer.
abstract: Heat shock protein 90 (HSP90), a molecular chaperone, plays important roles in cellular protection against various stressful stimuli and in the regulation of cellular growth and apoptosis. HSP90 has 4 different types of human isoforms; HSP90α, HSP90β, glucose related protein 94 (GRP94) and tumor necrosis factor (TNF) receptor-associated protein 1 (TRAP1). We assessed the differential expression of these HSP90 isoforms in small-cell lung cancer (SCLC) and the correlation of their expression levels with clinicopathological factors and patient survival rates. This study included 117 SCLCs, comprised of 108 primary and 9 metastatic tumor tissues. We performed immunohistochemical staining for HSP90α, HSP90β, GRP94 and TRAP1 in 117 tumors and found that HSP90α and HSP90β were positive in 11 (9%) and 61 tumors (52%), respectively, most of which showed weak expression, whereas GRP94 and TRAP1 were positive in 115 (98%) and 117 tumors (100%), respectively, the majority of which showed moderate or strong expression. None of the HSP90 isoforms showed significant associations with clinicopathological factors or survival status in patients with SCLC. Our results indicate that GRP94 and TRAP1 might contribute more to the carcinogenesis or biology of SCLC than HSP90α and HSP90β, and that isoform selectivity should be considered when HSP90 inhibitors are studied or utilized for the treatment of SCLC.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine Changwon, South Korea.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine Changwon, South Korea.
authors.forename: Kyung Woo
authors.initials: KW
authors.lastname: Kang
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine Changwon, South Korea.
authors.forename: Jeong-Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine Changwon, South Korea.
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Hwang
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine Changwon, South Korea.
authors.forename: Jae Hong
authors.initials: JH
authors.lastname: Park
authors.affiliation: Division of Hematology and Medical Oncology, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine Changwon, South Korea.
authors.forename: Seok-Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Division of Hematology and Medical Oncology, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine Changwon, South Korea.
authors.forename: Jun Ho
authors.initials: JH
authors.lastname: Ji
authors.affiliation: Department of Radiation Oncology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine Changwon, South Korea.
authors.forename: Tae Gyu
authors.initials: TG
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine Changwon, South Korea.
authors.forename: Hyun-Yeol
authors.initials: HY
authors.lastname: Nam
authors.affiliation: Department of Pathology, Dong-A University College of Medicine Busan, South Korea.
authors.forename: Mee Sook
authors.initials: MS
authors.lastname: Roh
authors.affiliation: Department of Pathology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine Changwon, South Korea.
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Lee
authors.affiliation: Department of Pathology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine Changwon, South Korea.
authors.forename: Moon-Il
authors.initials: MI
authors.lastname: Park
authors.affiliation: Department of Pathology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine Changwon, South Korea.
authors.forename: Mee-Seon
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Department of Pathology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine Changwon, South Korea.
authors.forename: Hyoun Wook
authors.initials: HW
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D020033:Protein Isoforms / Q000378:metabolism*; D055752:Small Cell Lung Carcinoma / Q000378:metabolism* / Q000473:pathology
chemical_list: D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D008565:Membrane Proteins; D020033:Protein Isoforms; C092306:TRAP1 protein, human; C018551:glucose-regulated proteins
keywords: GRP94; HSP90; Small cell lung cancer; TRAP1; immunohistochemistry; isoform