Analysis of apoptosis in human papillomavirus type 16 E7-expressing human head and neck epithelial cells -Enhancement of Fas-mediated apoptosis-
| Project/Area Number |
12671687
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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 |
Otorhinolaryngology
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| Research Institution | St. Marianna University School of Medicine |
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Principal Investigator |
TSUTSUMI Kouichiro St. Marianna University School of Medicine, Otolaryngology, Assistant Professor, 医学部, 講師 (40217344)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | HPV16 / Head and Neck epithelial cells / Apoptosis / pRb / 分化 / Fas / Bcl-X_L |
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| Research Abstract |
Retinoblastoma protein (pRb) is important in cell cycle control. pRb binds E2F and negatively regulates the transition from G1 to S phase by repressing genes responsive to the E2F family of transcription factors. Human papillomavirus type 16 E7 (E7) binds and inactivates the pRb. There are two mechanisms proposed for the inactivation of pRb by E7. One is that E7 physically interferes with pRb-E2F binding. The second mechanism is the targeted degradation of pRb. The purpose of this study was to examine the effects of E7-expression to Fas-mediated apoptosis in cultured human head and neck epithelial cells (HLECs). In Fas-sensitive cells, the apoptosis-inducing effect of Fas/Fas-ligand (FasL) binding is also observed when the anti-Fas antibody is bound to the Fas. We applied an anti-Fas antibody (CH11) to normal HLECs (nHLECs) and six E7-expressing HLECs (HLEC16E7), and monitored their cell death. All HLEC16E7a and nHLECs expressed Fas but not FasL. Five HLEC16E7s were more sensitive (CH11-sensitive), but one HLEC16E7 was less sensitive (CH11-resistant), to CH11-induced cell death compared to nHLECs. As compared to nHLECs, the levels of pRb were decreased in all HLEC16E7S, and the levels of wild-type p53 protein (p53) were increased in CH11-sensitive HLEC16H7s. [We have previously reported that the CH11-resistant HLEC16E7 had acquired a mutation (spontaneously mutated) of p53 gene (in codon 273 from CGT to CCT) and the five CH11-sensitive HLEC16E7s did not have p53 gene mutations within exon 4 to 8. -Acta Otolaryngol 522 : 94-98, 1996-]. These results suggest that E7-expression enhances the Fas-mediated apoptosis in HLECs. This enhanced response may be p53 dependent.
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Report
(4 results)
Research Products
(12 results)
