The role of TSC403/DC-Lamp gene in cervical carcinogenesis

• Project/Area Number: 16591656
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Osaka University
• Principal Investigator: ENOMOTO Takayuki Osaka University, Graduate School of Medicine, Lecture, 医学系研究科, 講師 (90283754)
• Co-Investigator(Kenkyū-buntansha): YOSHINO Kiyoshi Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (90362730) ; FUJITA Masami Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (60303963) ; 中嶌 竜一 大阪大学, 医学系研究科, 助手 (70335347) ; 上田 豊 大阪大学, 医学系研究科, 助手 (10346215) ; 岡澤 美佳 大阪大学, 医学部附属病院, 医員(臨床研究) ; 三宅 貴仁 大阪大学, 医学部附属病院, 医員(臨床研究)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000); Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
• Keywords: TSC403 / DC-Lamp / cervical cancer / metastases / invasion / prognostic / DC-Lamp

Research Abstract

In order to clarify the role of the TSC403/DC-Lamp gene in uterine cervical cancer, especially concerning metastasis, following experiments were designed. Quantitative RT-PCR showed TSC403/DC-Lamp mRNA expression was not detectable in normal uterine cervical tissue but highly expressed in uterine cervical cancer. In addition, high expression level of TSC403/DC-Lamp was significantly correlated with the overall survival of patients with stage I/II cervical cancer. These indicate that TSC403/DC-Lamp expression may be a prognostic molecule marker for cervical cancer. We also transfected a TSC403/DC-LAMP expression vector into a human uterine cervical cancer cell line, TCS. In vitro invasion assay showed the migration of TSC403/DC-LAMP-overexpressing TCS cells was significantly higher than in control TCS cells. In vivo metastasis assay demonstrated distant metastasis was significantly higher in TSC403/DC-lamp-overexpressing TSC cells than in control TCS cells. These results indicate that expression of TSC403/DC-Lamp associates with invasion and metastasis in uterine cervix cancer. Furthermore, we identified a promoter domain of a TSC403 gene to elucidate molecule mechanism of overexpression of a TSC403 gene. To examine the localization of TSC403/DC-Lamp protein in the cell, we have established the GFP-tagged vector and transfected to cervical cancer cell. TSC403/DC-Lamp protein was shown to be expressed specifically on a cell membrane in uterine cervix cancer cell.

Research Products

• [Journal Article] Overexpression of Lamp3/TSC403/DS-LAMP Promotes Metastasis in Uterine Cervical Cancer (2005)
  • Author(s): HiroyukiKanao, TakayukiEnomoto, ToshihiroKimura, MasamiFujita, RyuichiNakashima, Yutaka Ueda, Yuko Ueno, TakashiMiyatake, TatsuoYoshizaki, Gregory S.Buzard, AkiraTanigami, Kiyoshi Yoshino, YujiMurata
  • Journal Title: Cancer Res 65(19) Pages: 8640-8645
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Overexpression of Lamp3/TSC403/DC-LAMP Promotes Metastasis in Uterine Cervical Cancer (2005)
  • Author(s): Hiroyuki Kanao, Takayuki Enomoto, Toshihiro Kimura, Masami Fujita, Ryuichi Nakashima, Yutaka Ueda, Yuko Ueno, Takashi Miyatake, Tatsuo Yoshizaki, Gregory S.Buzard, Akira Tanigami, Kiyoshi Yoshino, Yuji Murata
  • Journal Title: Cancer Res, 200 65(19) Pages: 8640-8645
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Overexpression of LAMP3/TSC403/DC-LAMP Promotes Metastasis in Uterine Cervical Cancer (2005)
  • Author(s): Kanao H, Enomoto T, Kimura T, Fujita M, Nakashima R, Ueda Y, Ueno Y, Miyatake T, Yoshizaki T, Buzard GS, Tanigami A, Yoshino K, Murata Y.
  • Journal Title: Cancer Research 65(19) Pages: 8640-8650