Gene expression changes during HPV-mediated carcinogenesis: a comparison between an in vitro cell model and cervical cancer.


:We used oligonucleotide microarrays to investigate gene expression changes associated with multi-step human papillomavirus type 16 (HPV16)-mediated carcinogenesis in vitro. Gene expression profiles in 4 early passage HPV16-immortalized human keratinocyte (HKc) lines derived from different donors were compared with their corresponding 4 late-passage, differentiation-resistant cell lines, and to 4 pools of normal HKc, each composed of 3 individual HKc strains, on Agilent 22 k human oligonucleotide microarrays. The resulting data were analyzed using a modified T-test coded in R to obtain lists of differentially expressed genes. Gene expression changes identified in this model system were then compared with gene expression changes described in published studies of cervical intraepithelial neoplasia (CIN) and cervical cancer. Common genes in these lists were further studied by cluster analysis. Genes whose expression changed in the same direction as in CIN or cervical cancer (concordant) at late stages of HPV16-mediated transformation in vitro formed one major cluster, while those that changed in the opposite direction (discordant) formed a second major cluster. Further annotation found that many discordant expression changes involved gene products with an extracellular localization. Two novel genes were selected for further study: overexpression of SIX1 and GDF15, observed during in vitro progression in our model system, was confirmed in tissue arrays of cervical cancer. These microarray-based studies show that our in vitro model system reflects many cellular and molecular alterations characteristic of cervical cancer, and identified SIX1 and GDF15 as 2 novel potential biomarkers of cervical cancer progression.


Int J Cancer


Wan F,Miao X,Quraishi I,Kennedy V,Creek KE,Pirisi L




Has Abstract


2008-07-01 00:00:00












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    abstract::Previously, we have identified aloe-emodin (AE) as a new type of anticancer agent, with activity that is based on apoptotic cell death promoted by a neuroectodermal tumor-specific drug uptake. We attempt to clarify the intracellular target of AE and the apoptosis-signaling pathway activated by AE in neuroblastoma cell...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Pecere T,Sarinella F,Salata C,Gatto B,Bet A,Dalla Vecchia F,Diaspro A,Carli M,Palumbo M,Palù G

    更新日期:2003-10-10 00:00:00

  • Risk of invasive cervical cancer in relation to clinical investigation and treatment after abnormal cytology: a population-based case-control study.

    abstract::A substantial proportion of women with cervical cancer that have participated in cervical screening have a history of an abnormal cytology result. Our objective was to assess the impact of histological investigation and treatment of women with abnormal cytology on the subsequent risk of invasive cervical cancer. All i...

    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Silfverdal L,Kemetli L,Sparén P,Andrae B,Strander B,Ryd W,Dillner J,Törnberg S

    更新日期:2011-09-15 00:00:00

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    authors: Zeng J,Müller-Berghaus J,Nguyen XD,Klüter H,Schönhaber H,Song M,Schwinn N,Schadendorf D,Goerdt S,Eichmüller S,Dippel E

    更新日期:2006-11-15 00:00:00

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    journal_title:International journal of cancer

    pub_type: 杂志文章,meta分析


    authors: Riethdorf S,Frey S,Santjer S,Stoupiec M,Otto B,Riethdorf L,Koop C,Wilczak W,Simon R,Sauter G,Pantel K,Assmann V

    更新日期:2016-02-15 00:00:00

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    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Nordenvall C,Nilsson PJ,Ye W,Nyrén O

    更新日期:2011-01-01 00:00:00

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    journal_title:International journal of cancer

    pub_type: 杂志文章


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    更新日期:2006-12-01 00:00:00

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    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Hala M,Hartmann BL,Böck G,Geley S,Kofler R

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    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Siegfried JM,Kaufman DG

    更新日期:1983-10-15 00:00:00

  • Amplification of the EGF receptor and c-myc genes in human esophageal cancers.

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    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Lu SH,Hsieh LL,Luo FC,Weinstein IB

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  • Incidence and mortality from stomach cancer in Japan, Slovenia and the USA.

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    journal_title:International journal of cancer

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    authors: Pizarro GO,Zhou XC,Koch A,Gharib M,Raval S,Bible K,Jones MB

    更新日期:2007-06-01 00:00:00

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    pub_type: 杂志文章,评审


    authors: Sundlisaeter E,Dicko A,Sakariassen PØ,Sondenaa K,Enger PØ,Bjerkvig R

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    journal_title:International journal of cancer

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    journal_title:International journal of cancer

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    authors: Ghosh S,Ghosh A,Maiti GP,Alam N,Roy A,Roy B,Roychoudhury S,Panda CK

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    journal_title:International journal of cancer

    pub_type: 杂志文章


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    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: van der Flier S,Chan CM,Brinkman A,Smid M,Johnston SR,Dorssers LC,Dowsett M

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    journal_title:International journal of cancer

    pub_type: 杂志文章,多中心研究


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    更新日期:2009-07-01 00:00:00

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    journal_title:International journal of cancer

    pub_type: 杂志文章


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    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Shipova LY,Gleiberman AS

    更新日期:1985-01-15 00:00:00

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    journal_title:International journal of cancer

    pub_type: 杂志文章


    authors: Bulay O,Urman H,Patil K,Clayson DB,Shubik P

    更新日期:1979-01-15 00:00:00