| Project/Area Number |
03454467
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
外科・放射線系歯学
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| Research Institution | THE UNIVERSITY OF TOKUSHIMA |
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Principal Investigator |
SATO Mitsunobu UNIVERSITY OF TOKUSHIMA SCHOOL OF DENTISTRY, Professor, 歯学部, 教授 (00028763)
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| Co-Investigator(Kenkyū-buntansha) |
KAJI Ryoji UNIVERSITY OF TOKUSHIMA SCHOOL OF DENTISTRY, Assistant, 歯学部, 助手 (30204390)
AZUMA Masayuki UNIVERSITY OF TOKUSHIMA SCHOOL OF DENTISTRY, Instructor, 歯学部附属病院, 講師 (20144983)
YURA Yoshiaki UNIVERSITY OF TOKUSHIMA SCHOOL OF DENTISTRY, Instructor, 歯学部附属病院, 講師 (00136277)
YOSHIDA Hideo UNIVERSITY OF TOKUSHIMA SCHOOL OF DENTISTRY, Associate Professor, 歯学部, 助教授 (30116131)
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| Project Period (FY) |
1991 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1993: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1992: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1991: ¥4,900,000 (Direct Cost: ¥4,900,000)
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| Keywords | Human salivary gland cancer cells / Hexamethylene bisacetamide / 8-chloroadenosine 3' : 5'-cyclic monophosphate / Differentiation therapy / Protein kinase C / Protein kinase A / dibutyryl cAMP / DNA hypomethylation / Hexamethylene bisacetamide / 8-chloroadenosine 3':5'-cyclic monophosphate / 分化誘導 / 高転移性ヒト唾液腺癌細胞 / 不死化正常ヒト唾液腺細胞 / 唾液腺癌細胞 / ニューロフイラメント / グリア線維酸性蛋白 / エトポシド / 5-fluoro-2'-deoxyuridine / 高転移性唾液腺癌細胞 / 8ーchloro odenosine 3':5'ーcyclic monophosphate / プロテイン・キナ-ゼC / Hー7 |
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| Research Abstract |
1. Treatment by hexamethylene bisacetamide (HMBA) or 8-chloroadenosine 3' : 5' -cyclic monophosphate (8-Cl-cAMP) of human salivary gland cancer cells (HSG and HSY), which were grown in vitro and as xenograft in nude mouse, resulted in marked growth inhibition. 2. We have already found that be treatment of HSG cells with 5-azacytidine results in the differentiation into myoepithelial cells (HSG-AZA1) and acinar cells (HSG-AZA3). In the present study, we have found that differentiation into the neuron-like cells of HSG-AZA1 cells occurs in growth medium containing 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine(H-7), an inhibitor of protein kinase C.When the isoenzymic patterns of protein kinase C in HSG-AZA1 cells were analyzed, expression of all the 3 types of isoenzyme was found in the cells ; however, decreased expression of type II protein kinase C was observed in the HSG-AZA1 cells treated with H-7, as compared with untreated cells. In addition, we have found that treatment of HSG-AZA1 cells with dibutyryl cAMP results in the differentiation into neuron-like cells. 3. Treatment of HSG cells with HuIFN-a significantly decreased the number of EGF receptors/cell. 4. Treatment of HSG or HSG-AZA1 cells with HMBA resulted in the differentiation into glial cells, which was accompanied by the appearance of DNA hypomethylation and decreased expression of type II protein kinase C in the treated cells. 5. It has been suggested that selective binding of 8-Cl-cAMP to cAMP-dependent protein kinase A receptor present in HSG or HSY cells caused marked growth inhibition. 6. The cultivation of HSG cells in the presence of etoposide, an inhibitor of DNA topoisomerse II, resulted in the emergence of cells with a smooth muscle cell phenotype, such as expression of a-smooth muscle actin and myofilaments, which was accompanied by decreased expression of ras oncogene product as compared with the untreated cells. 7. We have prepared the metastasizing HSG cells (mHSG) by treating non-met
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