| Project/Area Number |
10670166
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Human pathology
|
|---|
| Research Institution | Kagoshima University |
|---|
Principal Investigator |
HASUI Kazuhisa Kagoshima University, Faculty of Medicine, Instructor, 医学部, 講師 (70198703)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SATO Eiichi Kagoshima University, Faculty of Medicine, Professor, 医学部, 教授 (60004579)
IZUMO Shuji Kagoshima University, Faculty of Medicine, Professor, 医学部, 教授 (30143811)
|
|---|
| Project Period (FY) |
1998 – 1999
|
| Project Status |
Completed (Fiscal Year 1999)
|
| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Keywords | Highly sensitive histochemistry / HTLV-1 / Tax / Rex / E2F / Cyclin E / ATLL / T-cell lymphoma / CyclinE / T-cell Lymphoma |
|---|
| Research Abstract |
This study aimed to see pathogenesis of HTLV-1-related diseases, especially adult T-cell leukemia/lymphoma (ATLL) by means of highly-sensitive histochemistry. Integrated HTLV-1 proviral DNA is the first target to be detected by means of the highly-sensitive histochemistry. But, because of degradation of DNA strands in paraffon sections of routinely processed tissue, the proviral DNA is not a good target to be detected in the sections. We established highly sensitive immunohistochemistry of HTLV-1 p40Tax (Tax), p27Rex (REx), and transcription factors in G1/S transition of cell cycle. By means of the highly-sensitive immunohistochemistry, the relation of expression of Tax and Rex and to the phenotypic transformation in ATLL cells, and to the expression of the transcription factors in G1/S transition of cell cycle. ATLL cells expressed much more Rex than Tax. ATLL cells did not expressed Tax in all phases of cell growth and proliferation. Highly-sensitive histochemical detection of Tax and Rex is useful in the differential diagnosis of ATLL from the other T-cell lymphomas. ATLL cells showed overexpression of one of E2F families in nucleus or no expression of them, whereas European cases of T-cell lymphomas without HTLV-1 infection showed overexpression of cyclin E. Expressing a small amount of Tax, ATLL cells expressed weakly cyclin E in asmall number of nuclei. Consequently, it was suggested that HTLV-1 leukemogenesis of ATLL focuses on the proliferation signal transduction system that ends to release E2F from retinoblastoma protein to nucleus in G1/S transition. On the other hand, ATLL cells suggested over-riding checkpoint abnormality in cell cycle, expressing a large amount of E2F in nuclei even in S phase of cell cycle in some cases. Tax expressed weakly expressed in ATLL cells was thought to induce weak expression of cyclin E in nucleus, although this expression of cyclin E is thought to be a part of preserved cell function.
|
