Up-regulation of human endogenous retroviruses (HERVs) sometimes occurs in cancer. This study identifies a novel HERV (HERV-HX) in colon tumor tissues. which is an H family HERV (HERV-H) element located on chromosome Xp22.32. The full-length transcript sequence was identified and characterized. Quantitative RT-PCR indicated it is up-regulated in colon tumor samples. Using RT-PCR to analyze the transcription of the env-deleted HERV-HX and other env-intact HERV-H elements, it was demonstrated that transcription of HERV-H in colon cancer is not associated with the env gene. A 17-bp sequence was found within the 5' U3 region of HERV-HX, and only 8-bp sequences existed on its homologous U3 regions in the corresponding loci. Promoter activity assays indicated that replacing the 17-bp sequence with an 8-bp sequence or deleting it reduced its activity, suggesting that the 17-bp sequence is important to the expression of HERV-HX. (C) 2009 Elsevier Inc. All rights reserved.