Cancer Center Member
Paula H Stern, PhD
Professor, Molecular Pharmacology and Biological Chemistry; Feinberg School of Medicine
Translational Research in Solid Tumors
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Cancer Focused Research:
My primary research relates to mediators and signaling pathways involved in hormone action on osteoblasts and osteoclasts, and their implications for osteoporosis, cancer metastases to bone and women's health.
In the area of prostate cancer, we have investigated the mechanism of the abnormal bone formation resulting from prostate cancer metastases. We have determined that conditioned media from LNCaP prostate cancer cells stimulates osteoblast proliferation and protein synthesis. The effects were found to be dependent upon insulin-like growth factor 1, acting through a MAP kinase pathway.
We have defined a novel parathyroid hormone/parathyroid hormone related peptide signaling pathway in osteoblasts functioning through the heterotrimeric protein Galpha 12, the small G protein RhoA and protein kinase C alpha. The pathway has effects on osteoblast survival, cytoskeletal integrity and regulation of the osteoclastogenic factor receptor activator of NFkB ligand (RANKL).
In studies in human osteoblasts, we have found that androgen markedly increases tumor necrosis factor-alpha in osteoblasts from male donors, whereas estrogen increases the RANKL receptor RANK in cells from female donors. The role of these effects in bone metastases in prostate and breast cancer are of interest.