Hypoxia is a hallmark of solid tumors. In response to hypoxic conditions, tumor cells adapt to the microenvironment by regulating metabolism, angiogenesis, cell motility and invasion and the balance between survival and cell death. High levels of HIF-1alpha are routinely detected in most solid cancers, and over-expression of HIF-1alpha has been shown to correspond with poor clinical outcome and resistance to radiation and chemotherapy.
The Seagroves Laboratory Focus
Our laboratory is focused on discovering how over-expression of the transcription factor Hypoxia-Inducible Factor (HIF)-1alpha by the breast tumor epithelium promotes breast cancer progression and metastasis. We are currently investigating how HIF-1alpha promotes cancer stem cell (or tumor-initiating cell) activity and metastasis in breast cancer using novel syngeneic cell lines developed in our laboratory. These cells were derived from each of three commonly utilized transgenic mouse models of breast cancer (MMTV-PyMT, MMTV-myc and MMTV-Neu) and are transplantable to immunocompetent recipients.
Ongoing Research Activities
We are also interested in determining if different subsets of HIF-1 target genes are responsible for mediating tumor progression versus metastasis and in investigating the contribution of novel, individual HIF-1-dependent target genes to breast cancer growth, progression and metastasis. And, we collaborate with several investigators to test the efficacy and safety of their novel therapeutic strategies against metastatic breast cancer using both pre-clinical mouse models and human cell lines.
More recently, we have begun to utilize transgenic fruit flies to understand how the HIF axis controls collective cell migration that occurs during border cell migration. These experiments are performed in collaboration with Dr. Lawrence T. Reiter, Dept. of Neurology, UTHSC and Director, UTHSC Fly Transgenic Core.