| Project/Area Number |
14570570
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Respiratory organ internal medicine
|
|---|
| Research Institution | Nippon Medical School |
|---|
Principal Investigator |
KUDOH Shoji Medical School, Professor, 大学院・医学研究科, 教授 (40256912)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
GEMMA Akihiko Medical School, Lecturer, 医学部, 講師 (20234651)
YOSHIMURA Akinobu Medical School, Lecturer, 医学部, 講師 (00230805)
|
|---|
| Project Period (FY) |
2002 – 2003
|
| Project Status |
Completed (Fiscal Year 2003)
|
| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
|
|---|
| Keywords | Idiopathic pulmonary fibrosis / Carcinogenesis / cDNA array / Smad4 / Transcriptional disorder / cDNA array / 肺癌 / 発がん / 遺伝子異常 / 遺伝子発現異常 |
|---|
| Research Abstract |
Patients with Idiopathic pulmonary fibrosis (IPF) have an increased risk of developing lung cancer. To identify the key molecules involved in malignant transformation in IPF, we analyzed the expression profiles of lung tumor and paired lung tissue from patients with lung cancer and IPF (lung cancer/IPF) by cDNA array. Reduced expression of the Smad4 gene was frequently identified in tumor samples from lung cancers/IPF patients in real-time RT-PCR. In addition, mutational analysis of TGF-β type II receptor and Smad4 genes and analysis of the methylation status of the Smad4 promoter were examined by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and methylation specific PCR (MSP) with subsequent sequencing analysis in this study. No mutation was detected in the eight tumor samples, but alterations of the Smad4 gene transcription were identified. Our findings indicated that Smad4 inactivation may play an important role in pulmonary carcinogensis or progression of lung cancer in IPF patients in which TGF-β is overexpressed, and that the alteration of Smad4 transcription may be one mechanism. These findings could be used to improve treatment of lung cancer patients with IPF.
|
