Secific regions of HPV16genome for human keratinocyte differentiation dentranscript
Project/Area Number |
09671769
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Otorhinolaryngology
|
Research Institution | St. Marianna University School of Medicine |
Principal Investigator |
TSUSUMI Kouichiro St.Marrianna University School of Medicine, Assistant Professor, 医学部, 講師 (40217344)
|
Project Period (FY) |
1997 – 1999
|
Project Status |
Completed (Fiscal Year 1999)
|
Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥1,400,000 (Direct Cost: ¥1,400,000)
|
Keywords | Human keratinocyte / Human papillomaviruses Type / Differentiation / Transcription / 転写制御 / HPV-16 |
Research Abstract |
The life cycle of human papillomaviruses (HPVs) are closely linked to the differentiation status of infected human keratinocytes (HKs), with viral gene transcription being maintained at low levels in undifferentiated HKs and increased upon host HK differentiation. The aim of this study was to detect specific regions of HPV16 genome for the differentiation-dependent transcription. A variety of physiological agents, including calcium (CaィイD12+ィエD1), induces the HK differentiation. I analyzed changes in the transcription pattern of HPV16 gene in two types of HPV16-containing HKs, HPV16-immortalized HKs (HLEC16 cells) and HPV16- positive (-infected) papilloma cells (HLP16 cells), during CaィイD12+ィエD1 induced differentiation. In HLEC16, the viral genes were integrated into the host cell chromosomes. In contrast, HLP16 contained multiple copies of the HPV16 DNA as episomes (extra-chromosomal viral genes). It has been reported that expression of cytokeratin No.13 (CK13) is marker for HK differ
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entiation. Both of HLP16 and HLEC16 responded to the increased CaィイD12+ィエD1 (0.1mM->1.0mM) with induction of CK13 expression. On the other hand, the level of viral RNA (E6+E7+E1 probe = nucleotides 57 to 866) was elevated in HLP16 by added CaィイD12+ィエD1 (1.0mM), but similar in HLEC16 grown under low- (0.1mM) or high- CaィイD12+ィエD1 (1.0mM) conditions. Signals with E6 probe [nucleotides (nt) 112 to 498] showed no change as HLP16 cell differentiation occurred (CaィイD12+ィエD1 = 1.0mM), while signals with E7 probe (nt 621 to 879) increased dramatically in the differentiated HLP16(CaィイD12+ィエD1 = 1.mM). These data suggest that a differentiation-inducible promoter leis between nt 498 (the 3' end of the E6 probe) and nt 879 (the 3' end of the E7 probe). Furthermore, this possible promoter appears to be active only when differentiating HKs contain episomal HPV16 DNA (the viral gene integration into the host cell chromosomes may be an important determinant resulting in the differentiation-independent transcription of HPV16 gene). Less
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Research Products
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