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Titolo:
Differential transcriptional regulation of the monocyte-chemoattractant protein-1 (MCP-1) gene in tumorigenic and non-tumorigenic HPV 18 positive cells: The role of the chromatin structure and AP-1 composition
Autore:
Finzer, P; Soto, U; Delius, H; Patzelt, A; Coy, JF; Poustka, A; zur Hausen, H; Rosl, F;
Indirizzi:
Deutsch Krebsforschungszentrum, Forschungsschwerpunkt Angew Tumorvirol, D-69120 Heidelberg, Germany Deutsch Krebsforschungszentrum Heidelberg Germany D-69120 lberg, Germany Forschungsschwerpunkt Genomforsch & Bioinformat, D-69120 Heidelberg, Germany Forschungsschwerpunkt Genomforsch & Bioinformat Heidelberg Germany D-69120
Titolo Testata:
ONCOGENE
fascicolo: 29, volume: 19, anno: 2000,
pagine: 3235 - 3244
SICI:
0950-9232(20000706)19:29<3235:DTROTM>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
NF-KAPPA-B; CERVICAL INTRAEPITHELIAL NEOPLASIA; HUMAN PAPILLOMAVIRUS INFECTION; JE GENE; HELA-CELLS; HYBRIDS; ALPHA; EXPRESSION; GROWTH; DNA;
Keywords:
chemokines; human papillomaviruses; cervical cancer; somatic cell hybrids; tumorigenicity;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Rosl, F Deutsch Krebsforschungszentrum, Forschungsschwerpunkt Angew Tumorvirol, Neuenheimer Feld 242, D-69120 Heidelberg, Germany Deutsch Krebsforschungszentrum Neuenheimer Feld 242 Heidelberg Germany D-69120
Citazione:
P. Finzer et al., "Differential transcriptional regulation of the monocyte-chemoattractant protein-1 (MCP-1) gene in tumorigenic and non-tumorigenic HPV 18 positive cells: The role of the chromatin structure and AP-1 composition", ONCOGENE, 19(29), 2000, pp. 3235-3244

Abstract

The expression of the monocyte-chemoattractant-protein-1 (MCP-1) is closely linked with a non-tumorigenic phenotype in somatic cell hybrids made between the human papillomavirus type 18 (HPV 18) positive cervical carcinoma cell line HeLa and normal human fibroblasts, In contrast, MCP-1 transcription is absent in tumorigenic segregants derived from the same hybrids or in parental HeLa cells. Selectivity of MCP-1 transcription, which is regulated at the le, el of initiation of transcription, is mainly based on differences in the location and extension of DNAse I-hypersensitive regions (DHSR) atboth ends of the gene, While TNF-alpha only moderately increases the sensitivity of pre-existing 5'-DHSRs, a 3'-end DHSR became strongly induced exclusively in non-malignant hybrids, DNA sequencing showed that the 3'-DHSR coincides with an additional AP-1 site located approximately 600 bp downstream of the polyadenylation site. Analyses of AP-1 composition revealed that MCP-1 is only expressed in those cells where jun-family members were mainly heterodimerized with the fos-related protein fra-1. In contrast, in tumorigenic cells the 1:1 ratio between jun and fra-1 is disturbed and the MCP-1 gene is no longer expressed. Hence, alterations in the heterodimerization pattern of AP-1 and its selective accessibility to opened chromatin may represent a novel regulatory pathway in the regulation of chemokines in malignant and non-malignant HPV-positive cells.

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Documento generato il 26/11/20 alle ore 10:23:35