Gene Expression Analysis of Preinvasive and Invasive Cervical Squamous Cell Carcinomas Identifies HOXC10 as a Key Mediator of Invasion
| Autor: | Cornelia L. Trimble, Rork Kuick, Bin Nan, Eric R. Fearon, Yali Zhai, Ichiro Ota, Kathleen R. Cho, Stephen J. Weiss |
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| Rok vydání: | 2007 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty Cell Uterine Cervical Neoplasms Cervix Uteri Chick Embryo Biology Cell Line Tumor Gene expression medicine Animals Humans Neoplasm Invasiveness RNA Small Interfering Cervix Oligonucleotide Array Sequence Analysis Homeodomain Proteins Cervical cancer Gene knockdown Gene Expression Profiling Cancer medicine.disease Gene Expression Regulation Neoplastic Gene expression profiling medicine.anatomical_structure Oncology Tumor progression Carcinoma Squamous Cell Female |
| Zdroj: | Cancer Research. 67:10163-10172 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | If left untreated, a subset of high-grade squamous intraepithelial lesions (HSIL) of the cervix will progress to invasive squamous cell carcinomas (SCC). To identify genes whose differential expression is linked to cervical cancer progression, we compared gene expression in microdissected squamous epithelial samples from 10 normal cervices, 7 HSILs, and 21 SCCs using high-density oligonucleotide microarrays. We identified 171 distinct genes at least 1.5-fold up-regulated (and P < 0.001) in the SCCs relative to HSILs and normal cervix samples. Differential expression of a subset of these genes was confirmed by quantitative reverse transcription-PCR and immunohistochemical staining of cervical tissue samples. One of the genes up-regulated during progression, HOXC10, was selected for functional studies aimed at assessing its role in mediating invasive behavior of neoplastic squamous epithelial cells. Elevated HOXC10 expression was associated with increased invasiveness of human papillomavirus–immortalized keratinocytes and cervical cancer–derived cell lines in both in vitro and in vivo assays. Cervical cancer cells with high endogenous levels of HOXC10 were less invasive after short hairpin RNA–mediated knockdown of HOXC10 expression. Our findings support a key role for the HOXC10 homeobox protein in cervical cancer progression. Other genes with differential expression in invasive SCC versus HSIL may contribute to tumor progression or may be useful as markers for cancer diagnosis or progression risk. [Cancer Res 2007;67(21):10163–72] |
| Databáze: | OpenAIRE |
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