HOXB7: An Oncogenic Gene in Breast Cancer Cells
Abstract
Homeobox genes control anterioposterior body axis patterning during development. Although expressed primarily in developing embryos, a growing body of evidence shows that homeobox gene re-expression in adult tissues is associated with tumorigenesis. Earlier work has shown that introduction of HOXB7, one of the members of this gene family, into non-expressing breast cancer cells induced expression of a number of pro-angiogenic factors and formed tumors upon xenograft into nude mice. Since a growing body of evidence showed that HOXR7 may be involved in ovarian, skin and breast cancer, we wanted to investigate its expression levels in breast carcinomas and evaluate its oncogenic potential in this study. To characterized the role of HOXB7 in breast cancer, a number of HOXB7-interacting proteins in breast cancer cells were identified and binding to HOXB7 was confirmed in vivo. Interestingly, all of the HOXB7-associated proteins identified have well characterized roles in the non-homologous end joining (NHEJ) pathway for DNA double strand break (DSB) repair as well as a larger role in maintenance of genomic integrity. Cell survival experiments demonstrated that breast cancer cells stably transfected with HOXB7 survive better after induction Df DNA DSB with fewer chromosomal abnormalities following exposure to gamma radiation. In addition, transduction of HOXB7 into the normal immortalized mammary epithelial cell line, MCFlOA, induced anchorage independent growth that was dependent of PARP activity. These data have led us to propose that HOXB7 may serve a role in breast cancer tumorigenesis in which PARP shares a common pathway.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2004
- Accession Number
- ADA430013
Entities
People
- Ethel Rubin
- Saraswati Sukumar
Organizations
- Johns Hopkins University