HOXB7: An Oncogenic Gene in Breast Cancer
Annual summary rept. 15 Apr 2004-14 Mar 2005
JOHNS HOPKINS UNIV BALTIMORE MD SCHOOL OF MEDICINE
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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 HOXB7 may be involved in ovarian, skin and breast cancers, we wanted to investigate its expression levels in breast carcinomas and evaluate its oncogenic potential in this study. To characterize 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 of DNA DSB with fewer chromosomal abnormalities following exposure to gamma radiation. HOXB7 overexpression in primary tumors occurs due to amplification of the gene. HOXB7 amplification correlates with poor prognosis. Thus it is possible that HOXB7 is a novel marker for identifying aggressive tumors.
- Medicine and Medical Research