Early genetic events in HPV immortalised keratinocytes

Cottage, Amanda; Dowen, Sally E.; Roberts, Ian; Pett, Mark R.; Stanley, Margaret

doi:10.1002/1098-2264(2000)9999:9999<::aid-gcc1060>3.0.co;2-x

Cited by 40 publications

(34 citation statements)

References 57 publications

(57 reference statements)

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“…Similar markers have been observed in HPV-transformed cell lines (Miller et al, 1971;Durst et al, 1987;Popescu et al, 1987;James et al, 1989;Smith et al, 1989;Macville et al, 1999). Gain of 5p, however, is not observed in low-grade lesions or HR HPV containing keratinocyte cell lines at early passage in vitro (Cottage et al, 2001). Amplification of the entire short arm of chromosome 5 suggests the presence of gene(s) whose gain of function seems to be highly advantageous in the progression towards advanced stage CaCx and in CaCx cell lines.…”

Section: Introductionsupporting

confidence: 52%

“…M-FISH data revealed amplification of chromosome 5 material to be a consistent event, as a result of small metacentric chromosome formation or translocation. Gain of 5p is a late event, observed in established cell lines but is not in HPV immortalized lines at early passage (Cottage et al, 2001). Single chromosome 5 painting confirmed these findings.…”

Section: Discussionmentioning

confidence: 99%

“…M-FISH analysis of eight new cell lines derived from CaCx biopsies and five established CaCx lines (see Table 1 Composite karyotypes for CaSki, SiHa and C33a determined by M-FISH analysis were reported previously by us (Cottage et al, 2001).…”

Section: M-fish Analysis Detects Structural Aberrations and Ploidy Chmentioning

confidence: 99%

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Amplification of chromosome 5p correlates with increased expression of Skp2 in HPV-immortalized keratinocytes

et al. 2003

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Section: Introductionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

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Amplification of chromosome 5p correlates with increased expression of Skp2 in HPV-immortalized keratinocytes

et al. 2003

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“…20 The GATA-3 gene is located at 10p15, a region, which is more than incidentally altered in HPV-immortalized cells and in cervical carcinomas. 4,[21][22][23][24][25][26] In addition, putative senescence and telomerase repressor loci have recently been identified at 10p14-p15 and 10p15, respectively. 27,28 Therefore, further functional studies are warranted to find out whether GATA-3 deregulation is involved in HPV-mediated immortalization and cervical carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

Down-Regulation of GATA-3 Expression during Human Papillomavirus-Mediated Immortalization and Cervical Carcinogenesis

Steenbergen

OudeEngberink

Kramer

et al. 2002

The American Journal of Pathology

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To identify cellular genes that may be involved in human papillomavirus (HPV)-mediated immortalization mRNA differential display analysis was performed on preimmortal and subsequent immortal stages of four human keratinocyte cell lines transformed by HPV type 16 or 18 DNA. This yielded a cDNA fragment encoding the transcription factor GATA-3 that was strongly reduced in intensity in all immortal stages of the four cell lines. A marked reduction in both GATA-3 mRNA and protein expression in HPV-immortalized cell lines was confirmed by reverse transcriptase-polymerase chain reaction, Western blot analysis, and immunohistochemistry and was also shown to be apparent in cervical carcinoma cell lines. Immunohistochemical analysis of cervical tissue specimens showed a clear nuclear staining for GATA-3 in normal cervical squamous epithelium (n ‫؍‬ 14) and all cervical intraepithelial neoplasia (CIN) I (n ‫؍‬ 6) and CIN II lesions (n ‫؍‬ 2). In contrast, 11% (1 of 9) of CIN III lesions and 67% (8 of 12) of cervical squamous cell carcinomas revealed a complete absence of GATA-3 immunostaining. Hence, complete down-regulation of GATA-3 expression represents a rather late event during cervical carcinogenesis. Whether GATA-3 down-regulation is etiologically involved in HPV-mediated immortalization and cervical carcinogenesis remains to be examined. Infection with high-risk human papillomavirus (HPV) types is the most significant risk factor for the development of cervical cancer and HPV DNA can be detected in almost all cervical squamous cell carcinomas. 1 HPV functions are, however, not sufficient for the development of cervical cancer and additive oncogenic events involving host cell genes are required, consistent with a multistep process of carcinogenesis. To gain better insight in HPV-mediated carcinogenesis in vitro model systems have been proven very valuable. High-risk HPV types, in particular HPV 16 and HPV 18, can induce immortalization of primary human epithelial cells in vitro. [2][3][4] Studies involving somatic cell fusions and microcell-mediated chromosome transfers have indicated that particularly recessive gene alterations are crucial for immortalization of HPV-containing epithelial cells. 5,6 HPV-mediated immortalization is associated with an arrest of telomeric shortening and activation of the telomere lengthening enzyme telomerase. 4,7 Moreover, activation of telomerase, by up-regulation of its catalytic subunit human telomerase reverse transcriptase gene, seemed to be necessary and sufficient for immortalization of HPV-transfected keratinocytes. 6,8,9 In addition, expression of the viral oncogene HPV 16 E6 from a heterologous promoter has been shown to activate telomerase in primary keratinocytes. 10 However, expression of HPV 16 and HPV 18 E6 from their native promoter in the context of the fulllength virus genome did not result in telomerase activation, 4 indicating that additive events are required.Recent studies have shown that yet unknown genes residing at chromosomes 3, 4, and 6 can regulate telomer...

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“…Metaphase spreads were hybridized with a chromosome 4 probe prepared from flowsorted chromosome 4 DNA and chromosome painting carried out as described previously (Cottage et al, 2001).…”

Section: Chromosome Paintingmentioning

confidence: 99%

Functional evidence for a squamous cell carcinoma mortality gene(s) on human chromosome 4

et al. 2002

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Early genetic events in HPV immortalised keratinocytes

Cited by 40 publications

References 57 publications

Amplification of chromosome 5p correlates with increased expression of Skp2 in HPV-immortalized keratinocytes

Amplification of chromosome 5p correlates with increased expression of Skp2 in HPV-immortalized keratinocytes

Down-Regulation of GATA-3 Expression during Human Papillomavirus-Mediated Immortalization and Cervical Carcinogenesis

Functional evidence for a squamous cell carcinoma mortality gene(s) on human chromosome 4

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