2002 Fiscal Year Final Research Report Summary
Identification of target genes within an amplicon at 14ql2-21 in esophageal squamous cell carcinoma
| Project/Area Number |
13670497
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Gastroenterology
|
|---|
| Research Institution | Tokyo Medical & Dental University |
|---|
Principal Investigator |
YASUI Kohichiroh Medical Research Institute, Assistant Professor, 難治疾患研究所, 助手 (30323695)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
INAZAWA Johji Medical Research Institute, Professor., 難治疾患研究所, 教授 (30193551)
|
|---|
| Project Period (FY) |
2001 – 2002
|
| Keywords | Esophageal cancer / Gene amplification / Cancer associated gene / Hepatocellular carcinoma / Small cell lung cancer |
|---|
| Research Abstract |
Comparative genomic hybridization (CGH) studies have revealed frequent amplification of the 14q12-q21 region in esophageal squamous cell carcinoma (ESC) cell lines. To identify genes targeted for amplification, we first defined the minimal common region of amplification using fluorescence in situ hybridization in affected ESC cell lines. The amplicon covered about 6 Mb, between markers D14S1034 and L18528. Five known genes (BAZ1A, SRP54, NFKBLA, MBIP, and HNF3A) and two uncharacterized ESTs (GenBank Accession numbers AA991861 and AA167732) within the amplicon showed amplification and consequent over-expression (Gene Chromosomes Cancer, 2001).
We demonstrated that three genes, TFDP1, CUL4A, and CDC16, were probable targets for amplification at 13q34 in hepatocellular cacinomas. TFDP1 over-expression led to up-regulation of cyclin E, a positive regulator for cell cycle G1/S transition (Hepatology, 2002). Moreover we identified SKP2 as a target within the 5pl3 amplicon that was frequently detected in small cell lung cancers (SCLCs). SKP2 positively regulates progression of cell cycle by targeting several regulators, such as the cell-cycle inhibitor p27^<KIP1> for ubiquitin-mediated degradation. Down-regulation of SKP2 using an antisense oligonucleotide remarkably suppressed the growth of SCLC cells, indicating that SKP2 played an important role in the growth of SCLC cells (Am J Pathol, 2002).
|
Research Products
(6 results)
