Molecular Genetics of the Heterogeneiety of the Tumor Perturbing Cacer Treatment

• Project/Area Number: 16390381
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: KYUSHU UNIVERSITY
• Principal Investigator: INOUE Hiroshi Kyushu University, Medical Institute of Bioregulation, Department of Molecular and Cellular Biology, Associate Professor, 生体防御医学研究所, 助教授 (90203249)
• Co-Investigator(Kenkyū-buntansha): MIMORI Koshi Kyushu University, Medical Institute of Bioregulation, Department of Molecular and Cellular Biology, Research Associate, 生体防御医学研究所, 助手 (50322748) ; TANAKA Fumiaki Kyushu University, Hospital, Department of Molecular and Cellular Biology, Research Associate, 大学病院, 助手 (30332836)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥14,300,000 (Direct Cost: ¥14,300,000); Fiscal Year 2005: ¥6,900,000 (Direct Cost: ¥6,900,000); Fiscal Year 2004: ¥7,400,000 (Direct Cost: ¥7,400,000)
• Keywords: Cancer / Heterogeneity / DNA microarray / LMD / Gastric cancer / Hepatocellular carcinoma / Laser pressure cell transfer method / Genome array / laser pressure cell transfer metho

Research Abstract

Purpose
To investigate the genetic base of the heterogeneity of the digestive cancer, two approaches such as 1)DNA microarray analysis combined with laser microdissection for the gene expression of the digestive tract carcinoma and 2)cancer stem cell survey have been conducted.
Material and method
Cell line and clinically resected tumor specimens were used for the analysis. Human 44k-DNA microarray were purchased from "Agilent technology" and microarray analysis were performed according to the company's instruction. In addition, genomic microarray were performed for 10 cases of esophageal cancer and 5 cased of hepatocellular carcinoma.
Results
1)Early staged cancer shows no definitive different expression profile from various parts of the tumor, however, in advance staged cancer, a definitive difference of the profile was observed among the portions of the tumor, in particular, superficial luminal parts and deeper invasive portions.
2)Expression profiles differ in cases with different histological types.
3)Genomic alteration and simultaneous mRNA expression changes were observed in accordance with the histological development of the tumor. In hepatocellular carcinoma, peripheral portion of the tumor shows very faint alteration in both mRNA and genomics. However, in the central portion that reciprocally later developed, histologically showed more aggressive pattern and also manifested very variable alterations in both mRNA and genomics.
Discussion
DNA microarray analysis combined with laser microdissection for the gene expression as well as genomic alteration had very powerful potential for the analysis of histologically complexed tumor. More detailed study will clarify the perplexed nature of the human carcinogenesis.

Research Products

• [Journal Article] Significance of skp2 expression in primary breast cancer (2006)
  • Author(s): Sonoda H. et al.
  • Journal Title: Clin Cancer Res 12 Pages: 1215-1220
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] FHIT Is Up-Regulated by Inflammatory Stimuli and Inhibits Prostaglandi E2-Mediated Cancer Progression (2006)
  • Author(s): Mimori K. et al.
  • Journal Title: Cancer Res 66 Pages: 2683-2690
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Significance of skp2 expression in primary breast cancer. (2006)
  • Author(s): Sonoda, H., Inoue, H., Ogawa, K., Utsunomiya, T., Masuda, T.A., Mori, M.
  • Journal Title: Clin Cancer Res 12 Pages: 1215-1220
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] FHIT is up-regulated by inflammatory stimuli and inhibits prostaglandin E2-mediated cancer progression. (2006)
  • Author(s): Mimori, K., Ishii, H., Nagahara, H., Sudo, T., Yamashita, K., Inoue, H., Barnard, G.F., Mori, M.
  • Journal Title: Cancer Res 66 Pages: 2683-2690
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Genetic susceptibility of catechol-O-methyltransferase polymorphism in Japanese patients with breast cancer (2005)
  • Author(s): Inoue, H., et al.
  • Journal Title: Oncol Rep 14 Pages: 707-712
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Clinical significance of human kallikrein gene 6 messenger RNA expression in colorectal cancer. (2005)
  • Author(s): Ogawa, K et al.
  • Journal Title: Clin Cancer Res 11 Pages: 2889-2893
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Global Analysis of Altered Gene Expressions during the Process of Esophageal Squamous Cell Carcinogenesis in the Rat : A Study Combined with a Laser Microdissection and a cDNA Microarray. Cancer (2005)
  • Author(s): Nishida K. et al.
  • Journal Title: Cancer Res 65 Pages: 401-409
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] N-cadherin is regulated by activin A and associated with tumor aggressiveness in esophageal carcinoma (2005)
  • Author(s): Inoue, H. et al.
  • Journal Title: Clin Cancer Res 10 Pages: 5702-5707
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Genetic susceptibility of catechol-O-methyltransferase polymorphism in Japanese patients with breast cancer. (2005)
  • Author(s): Inoue, H., Shibuta, K., Matsuyama, A., Yoshinaga, K., Sadanaga, N., Ueo, H., Barnard, G.F., Mori, M.
  • Journal Title: Oncol Rep 14 Pages: 707-712
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Clinical significance of human kallikrein gene 6 messenger RNA expression in colorectal cancer. (2005)
  • Author(s): Ogawa, K., Utsunomiya, T., Mimori, K., Tanaka, F., Inoue, H., Nagahara, H., Murayama, S., Mori, M.
  • Journal Title: Clin Cancer Res 11 Pages: 2889-2893
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Global analysis of altered gene expressions during the process of esophageal squamous cell carcinogenesis in the rat : a study combined with a laser microdissection and a cDNA microarray. (2005)
  • Author(s): Nishida, K., Mine, S., Utsunomiya, T., Inoue, H., Okamoto, M., Udagawa, H., Hanai, T., Mori, M.
  • Journal Title: Cancer Res 65 Pages: 401-409
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] N-cadherin is regulated by activin A and associated with tumor aggressiveness in esophageal carcinoma. (2005)
  • Author(s): Inoue, H., Yoshinaga, K., Utsunomiya, T., Sonoda, H., Masuda, T., Mimori, K., Tanaka, Y., Mori, M.
  • Journal Title: Clin Cancer Res 10 Pages: 5702-5707
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Global Analysis of Altered Gene Expressions during the Process of Esophageal Squamous Cell Carcinogenesis in the Rat : A Study Combined with a Laser Microdissection and a cDNA Microarray. (2005)
  • Author(s): Nishida K. et al.
  • Journal Title: Cancer Res 65 Pages: 401-409
• [Journal Article] The high expression of Fractalkine results in a better prognosis for colorectal cancer patients. (2005)
  • Author(s): Ohta M et al.
  • Journal Title: Int J Oncol 26 Pages: 41-47
• [Journal Article] Clinical significance of the overexpression of the candidate oncogene CYP24 in esophageal cancer (2004)
  • Author(s): Mimori k et al.
  • Journal Title: Ann Oncol 15 Pages: 236-241
• [Journal Article] A gene-expression siguiture can quantify the degree of hepatic fibrosis in the rat (2004)
  • Author(s): Utsunomiya T et al.
  • Journal Title: J Hepatol 41 Pages: 399-406
• [Journal Article] Defferential expression of MMP and uPA systems and prognostic relevance of their expression in esophageal squamous cell carcinoma (2004)
  • Author(s): Yamashita K et al.
  • Journal Title: Int J Cancer 110 Pages: 201-207
• [Journal Article] N-cadherin is regulated by activin A and Associated with tumor aggressiveness in esophageal carcinoma (2004)
  • Author(s): Inoue H. et al.
  • Journal Title: Clin Cancer Res 10 Pages: 5702-5707