{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T22:18:30Z","timestamp":1761862710826},"reference-count":65,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2007,10,24]],"date-time":"2007-10-24T00:00:00Z","timestamp":1193184000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2008,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Although high\u2010risk human papillomavirus (HPV) infection plays a major role in the development of cervical cancer, additive oncogenic events are involved as well. One key event involves increased activity of telomerase resulting from a deregulated expression of its catalytic subunit hTERT. Our previous microcell\u2010mediated chromosome transfer studies revealed that introduction of human chromosome 6 in the HPV16\u2010immortalized keratinocyte cell line FK16A and in the HPV16\u2010containing cervical cancer cell line SiHa induced growth arrest, resulting from a repression of hTERT mRNA expression and telomerase activity. Here, this model was used to analyze expression profiles associated with hTERT deregulation in HPV\u2010transformed cells. Microarray expression analysis of 12 FK16A\/chromosome 6 hybrids, 4 of which were negative for endogenous hTERT and 8 of which were positive for endogenous hTERT, resulted in the identification of 164 differentially expressed genes. Differential expression of a selection of 5 genes was verified by real\u2010time RT\u2010PCR. Of these 164 genes, 32 were also differentially expressed in other HPV transformed cells with deregulated hTERT. For 2 of these genes, encoding AQP3 and MGP, altered expression in hTERT positive cervical carcinomas was confirmed by real\u2010time RT\u2010PCR and immunohistochemistry, respectively. Moreover, increased MGP protein expression was significantly more frequent in high\u2010grade cervical premalignant lesions with elevated hTERT mRNA expression compared to those without. In summary, we identified 32 candidate biomarkers for deregulated hTERT mRNA expression, which may enable the identification of cervical premalignant lesions that are at highest risk to progress to invasive cancer. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.23210","type":"journal-article","created":{"date-parts":[[2007,10,24]],"date-time":"2007-10-24T17:21:20Z","timestamp":1193246480000},"page":"877-888","source":"Crossref","is-referenced-by-count":25,"title":["Gene expression profiling to identify markers associated with deregulated hTERT in HPV\u2010transformed keratinocytes and cervical cancer"],"prefix":"10.1002","volume":"122","author":[{"given":"Jillian","family":"de Wilde","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saskia M.","family":"Wilting","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris J.L.M.","family":"Meijer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark A.","family":"van de Wiel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bauke","family":"Ylstra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter J.F.","family":"Snijders","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renske D.M.","family":"Steenbergen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2007,10,24]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa021641"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2004.11.019"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc798"},{"key":"e_1_2_6_6_2","first-page":"3812","article-title":"Telomerase activity exclusively in cervical carcinomas and a subset of cervical intraepithelial neoplasia grade III lesions: strong association with elevated messenger RNA levels of its catalytic subunit and high\u2010risk human papillomavirus DNA","volume":"58","author":"Snijders PJ","year":"1998","journal-title":"Cancer Res"},{"key":"e_1_2_6_7_2","first-page":"1558","article-title":"Expression of human telomerase subunits and correlation with telomerase activity in cervical cancer","volume":"58","author":"Takakura M","year":"1998","journal-title":"Cancer Res"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1101\/SQB.1994.059.01.035"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7544491"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80538-3"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1053\/hupa.2000.19299"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2003.013730"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1159\/000059710"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.56.1.31"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1998.16.6.2238"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19980401)82:7<1319::AID-CNCR15>3.0.CO;2-9"},{"key":"e_1_2_6_17_2","first-page":"1249","article-title":"Transition of human papillomavirus type 16 and 18 transfected human foreskin keratinocytes towards immortality: activation of telomerase and allele losses at 3p, 10p, 11q and\/or 18q","volume":"13","author":"Steenbergen RD","year":"1996","journal-title":"Oncogene"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1006\/gyno.1997.4757"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/380079a0"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.2002.1542"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.1134"},{"key":"e_1_2_6_22_2","first-page":"7118","article-title":"Evidence for a putative senescence gene locus within the chromosomal region 10p14\u2010p15","volume":"61","author":"Poignee M","year":"2001","journal-title":"Cancer. 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