1998 Fiscal Year Final Research Report Summary
Development of Differentiation-directed Cancer Gene Therapy with p21
| Project/Area Number |
09671310
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Okayama University |
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Principal Investigator |
HIZUTA Akio Okayama University Medical School, Assistant Professor, 医学部, 講師 (60199007)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIWARA Toshioshi Okayama University Medical School, Instructor, 医学部, 助手 (00304303)
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| Project Period (FY) |
1997 – 1998
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| Keywords | p21 Gene / Differentiation / Gene Therapy |
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| Research Abstract |
A cycline-dependent kinase inhibitor p21 is induced in thc process of differentiation. To develop a novel gene-based anti-cancer therapy that can induce a welI-differentiated state in cancer cells, we examined antitumor offeet of the p21 gene transfer on human cancer cells. A recombinant adenovirus-mediated transient overexpression of p21 on TE-1 human esophageal cancer cells exhibited morphological changes indicative of differentiation, such as enlarged nuclei and flattened shape. Moreover, expression of involucrin protein, a differentiation marker of squamous cells, was up-regulated after the p21 gene transfer. We also found that retinoic acid receptor (RAR) was positively regulated by the p21 gene transfer in DLD-1 (colon), 1-11299 (lung), H460 (lung), and TE-13 (esophagus) human cancer cell lines. Increased expression of RAR induced the sensitivity to retinoic acid (RA) in RA-resistant DLD-1 cancer cells, resulting in the synergistic antitumor effect of the p21 gene transfer and RA treatment. These observations suggest that adenovirus-mediated p21 gene transfer can induce differentiation in human cancer cells and that the p21 gene has important implications for a differentiation-directed molecular therapy.
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[Publications] Kagawa, S., Fujiwara, T., Hizuta, A., Yasuda, T., Zhang, W.-W., Roth, J.A., Tanaka, N.: "p53 expression overcomes p21^<WAF1/CIP1>-mediated G1 arrest and induces apoptosis in human cancer cells." Oncogene. 15. 1903-1909 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kagawa, S., Fujiwara, T., Kadowaki, Y., Hizuta, A., Roth, J.A., Tanaka, N.: "Overexpression of the p21^<sdi 1> gene induces a senescence-like state in human cancer cells : Implication for senescence-directed molecular therapy for cancer." Cell Death Diff.(in press). (1999)
Description
「研究成果報告書概要(欧文)」より
