This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhai, Y. Articles by Cho, K. R. Search for Related Content PubMed PubMed Citation Articles by Zhai, Y. Articles by Cho, K. R.

Gene Expression Analysis of Preinvasive and Invasive Cervical Squamous Cell Carcinomas Identifies HOXC10 as a Key Mediator of Invasion

Departments of ¹ Pathology and ² Internal Medicine, and ³ The Comprehensive Cancer Center, The University of Michigan Medical School; ⁴ Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan; and ⁵ Department of Gynecology and Obstetrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland

Requests for reprints: Kathleen R. Cho, Department of Pathology, University of Michigan Medical School, 1506 BSRB, 109 Zina Pitcher, Ann Arbor, MI 48109-2200. Phone: 734-764-1549; Fax: 734-647-7950; E-mail: kathcho{at}umich.edu.

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]

This article has been cited by other articles:

				C. Klausen, P. C.K. Leung, and N. Auersperg Cell Motility and Spreading Are Suppressed by HOXA4 in Ovarian Cancer Cells: Possible Involvement of {beta}1 Integrin Mol. Cancer Res., September 1, 2009; 7(9): 1425 - 1437. [Abstract] [Full Text] [PDF]

				Z.-D. Gu, L.-Y. Shen, H. Wang, X.-M. Chen, Y. Li, T. Ning, and K.-N. Chen HOXA13 Promotes Cancer Cell Growth and Predicts Poor Survival of Patients with Esophageal Squamous Cell Carcinoma Cancer Res., June 15, 2009; 69(12): 4969 - 4973. [Abstract] [Full Text] [PDF]