This Article Full Text Full Text (PDF) Supplementary Data All Versions of this Article: 0008-5472.CAN-08-4546v1 69/12/4969    most recent 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 Google Scholar Articles by Gu, Z.-D. Articles by Chen, K.-N. PubMed PubMed Citation Articles by Gu, Z.-D. Articles by Chen, K.-N.

HOXA13 Promotes Cancer Cell Growth and Predicts Poor Survival of Patients with Esophageal Squamous Cell Carcinoma

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Departments of ¹ Thoracic Surgery I, and ² Genetics, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, P.R. China; and ³ Department of Gynecology and Obstetrics, Union Hospital of Fujian Medical University, Fuzhou, P.R. China

Requests for reprints: Ke-Neng Chen, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery I, Peking University School of Oncology, Beijing Cancer Hospital and Institute. No. 52 Fucheng Road, Haidian District, Beijing 100036, P.R. China. Phone: 86-10-8819-6536; Fax: 86-10-8819-6526; E-mail: chenkeneng{at}yahoo.com.cn.

Key Words: Esophageal cancer • Gene expression • Carcinogenesis • RNA expression • Immunohistochemistry

Homeobox genes are known to be classic examples of the intimate relationship between embryogenesis and tumorigenesis. Here, we investigated whether inhibition of HOXA13, a member of the homeobox genes, was sufficient to affect the proliferation of esophageal cancer cells in vitro and in vivo, and studied the association between HOXA13 expression and survival of patients with esophageal squamous cell carcinoma (ESCC). HOXA13 expression was permanently knocked down using an RNA interference technique, and cell strain with stable knockdown of HOXA13 protein was established. Colony formation assay showed that the number of colonies in HOXA13 protein–deficient cells was significantly less than that of control cells (P < 0.01). Tumor growth in nude mice showed that the weight and volume of tumors from the HOXA13 knockdown cells was significantly less than that from the control cells (P < 0.01). Then, HOXA13 expression in ESCC specimens and paired noncancerous mucosa was detected by immunohistochemistry, and overexpression of HOXA13 was found to be more pronounced in ESCCs than paired noncancerous mucosa (P < 0.05). Furthermore, the association of HOXA13 expression and disease-free survival time was analyzed in 155 ESCC cases. The median survival time of patients expressing HOXA13 was significantly shorter than HOXA13-negative patients (P = 0.0006). Multivariate analysis indicated that tumor-node-metastasis (TNM) stage and HOXA13 expression were independent predictors of disease-free survival time of patients with ESCC. Our results showed that HOXA13 expression enhanced tumor growth in vitro and in vivo, and was a negative independent predictor of disease-free survival of patients with ESCC. [Cancer Res 2009;69(12):4969–73]