WASHINGTON, DC USA (UroToday.com) - Dr. Sara Sukumar discussed chemotherapy resistant mechanisms in breast cancer.
HOX genes are molecular architects in development, as originally described by E.B. Lewis in the Developmental Genetics of Drosophila. They have highly conserved across evolution and time and they act like a set of molecular dominoes. Their concentrations of HOX proteins and their location of production and timing of activity in the body and target gene specificity result in differential development.
She focused on breast development, which occurs after birth and is a continuous process. She asked whether HOX genes are involved in breast development and cancer. Expression of HOXB7 in MCF-7 cells confers aggressive breast tumor growth properties. They can grow without estrogen. ER-positive breast cancers develop resistance to tamoxifen via alterations in signaling, co-regulators and mutations in ER. Thus, an EGRF/HER2 or mTOR inhibitor with tamoxifen has been used to treat tamoxifen-resistant tumors. She asked if it is possible to destroy all the pathways leading to tamoxifen resistance by targeting just one upstream gene, and could HOXB7 be such a gene? There are two HOXB7 binding sites in the EGFR promoter. HOXB7 overexpression results in activation of MAPK and AKT. Overexpression of HOXB7 results in upregulation of ER and this can be inhibited with use of fulvestrant. In a HOXB7 expressing cell line, suppression of HOXB7 was inhibitory. She concluded that HOXB7 may be an important target in breast cancer.
Presented by Sara Sukumar, PhD at the Society for Basic Urologic Research (SBUR)/Society of Urologic Oncology (SUO) joint meeting during the American Urological Association (AUA) Annual Meeting - May 14 - 19, 2011 - Walter E. Washington Convention Center, Washington, DC USA
Reported for UroToday by Christopher P. Evans, MD, FACS, Professor and Chairman, Department of Urology, University of California, Davis, School of Medicine.
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