Identification of Female-Specific Transcriptional Factors for Osteopontin Translation as a Host Factor to Determine the Difference of Clinical Features of Liver Diseases between Male and Female Patients

2011 Fiscal Year Final Research Report

• Project/Area Number: 21590858
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Saitama Medical University
• Principal Investigator: MOCHIDA Satoshi 埼玉医科大学, 医学部, 教授 (20219968)
• Co-Investigator(Kenkyū-buntansha): INAO Mie 埼玉医科大学, 医学部, 講師 (70286037) ; SUGAWARA Kayoko 埼玉医科大学, 医学部, 助教 (20406458)
• Project Period (FY): 2009 – 2011
• Keywords: オステオポンチン / 転写因子 / 性差 / エストロゲン / C型慢性肝炎 / SNP

Research Abstract

Osteopontin promoter SNPs(nt-155,-433) were responsible for the development of sexual difference of carcinogenesis in the liver. Promoter assay using male HepG2 cells and female MCF-7 cells revealed that the activities differed between alleles of either of SNPs in both cells. Also, gel-shift assay with nuclear extracts from both cells showed 3 signals ; a common signal for both cells, male-specific SRY and a female-specific indeterminate signal. The intensity of a common signal was different between the allele of nt-155, and that of a female-specific signal was increased following addition of estrogen to MCF-7 cells. These observations suggest that sexual difference of carcinogenesis may develop through these transcriptional factors which play differently between male and female cells.

Research Products

• [Presentation] Estrogen-dependent novel transfer factor as well as SRY may be involved in the sexual differrence in the development of hepatocellular carcinoma in HCV-infected patients through osteopontin expression in the liver (2010)
  • Author(s): Hamaoka K, Nagoshi S, Sugawara K, Inao M, Naiki K, Nakayama N, Fujiwara K, Mochida S
  • Organizer: 61^<st> Annual Meeting of American Association for the Study of the Liver
  • Place of Presentation: Boston, USA
  • Year and Date: 20101030-1102
• [Presentation] 肝病態における性差: Osteopontin遺伝子promoter SNPsに関連する新規転写因子のエストロゲンによる調節機構 (2010)
  • Author(s): 濱岡和宏, 名越澄子, 菅原通子, 内木佳代子, 稲生実枝, 中山伸朗, 藤原研司, 持田智
  • Organizer: 第46回日本肝臓学会総会
  • Place of Presentation: 山形
  • Year and Date: 20100627-28
• [Presentation] An unknown transfer factor up-regulated by estrogen may be involved in the sexual difference in the development of hepatocellular carcinoma in HCV-infected patients through osteopontin expression in the liver (2010)
  • Author(s): Hamaoka K, Nagoshi S, Sugawara K, Inao M, Naiki K, Nakayama N, Fujiwara K, Mochida S
  • Organizer: 45th Annual Meeting of European Association for the Study of the Liver
  • Place of Presentation: Wien, Austria
  • Year and Date: 20100414-18
• [Presentation] A novel transfer factor specific to female cells may be involved in the sexual difference in the development of hepatocellular carcinoma in HCV-Infected patients through osteopontin expression in the liver (2009)
  • Author(s): Hamaoka K, Nagoshi S, Sugawara K, Inao M, Naiki K, Nakayama N, Fujiwara K, Mochida S
  • Organizer: 60th Annual Meeting of American Association for the Study of Liver Diseases
  • Place of Presentation: Boston, USA
  • Year and Date: 20091030-1103