References:
- Ran Xie, David S. Loose, Gregory L.Shipley, Susu Xie, Roland L. Bassett Jr.,
Russell R. Broaddus Hypomethylation Induced Expression of S100A4 in Endometrial Carcinoma (2007) Modern Pathology, in press. - McCampbell, A.S., Bradduss, R.R., Loose, D.S., Davies, P.J.A. Overexpression of the Insulin-Like Growth Factor I Receptor and Activation of AKT in Hyperplastic Endometrium (2006). Clin Cancer Res 12(21): 6373-6378.
- Deng, L., Broaddus, R, McCampbell, A., Shipley, G..L., Loose, D.S., Stancel, G.M., Pickar, J.H., and Davies, P.J.A., . Identification of a Novel Estrogen Regulated Gene (EIG121) that is Induced by Hormone Replacement Therapy and Differentially Expressed in Type I and Type II Endometrial Cancer. Cancer Res. (2005) Dec 1;11(23):8258-64
David S. Loose, Ph.D.
Associate Professor
UTHSC, Medical School, (713) 500 - 7440
David.S.Loose@uth.tmc.edu
Signaling Pathways Involved in Endometrial Cancer
IIn general terms, my laboratory is interested in mechanisms that control gene expression and cell growth. Over the last few years, we have focused on identifying genes that are aberrantly expressed in endometrial cancer, which is the most common gynecologic cancer. To do this we employ several approaches including DNA and RNA microarray analysis of normal and malignant endometrium. We have determined that many signaling pathways can influence the rate of growth in the endometrium. One of these pathways is the wnt-signaling pathway. Wnts are glycoproteins that act a ligands; they interact with cell-surface receptors called frizzled that can produce downstream signals. This system is very complex: there are 19 wnts, 10 frizzleds, several antagonists such as sFRP, and a least 3 downstream pathways. The illustration depicts the “canonical” pathway that is mediated by wnt-induced stabilization of ß-catenin, but wnts can also indice signals via the “planar” polarity pathway, mediated by jun kinase, and the “calcium” pathway, mediated by NF-AT. Abnormal signals in any of these pathways can lead to disease. We have found that alteration of the canonical signals can leads to abnormal growth in the endometrium. We can detect early cancer by measuring the levels of expression of several genes. One of the best of these biomarkers is sFRP4 (secreted Frizzled-Related Protein). sFRP’s (there are 5 in humans, sFRP1-5). We have found that sFRP4 is expression is reduced nearly by 90% in tumors compared to normal endometrium. This lead us to examine the role of sFRP4 in regulating cell growth and we found that elevating expression of sFRP4 had a profound inhibitory effect on growth of a model endometrial cell line. We are currently performing studies to determine if sFRP is in fact a tumor-supressor.
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