16 K Prolactin as an Angiogenic Inhibitor in Breast Cancer
Annual rept. 1 Jun 99-31 May 00
CINCINNATI UNIV OH
Pagination or Media Count:
Tumors must induce the formation of new blood vessels to grow and metastasize. Prolactin PRL is a 23 kDa hormone that has mitogenic, morphogenic, and lactogenic actions on the breast, but its role in breast cancer is unclear. Its N-terminal 16K fragment suppresses endothelial cell proliferation in vifro, but its ability to inhibit tumor growth has not been tested. Highly specific antibodies against hPRL were generated and used to develop a novel dot blotchemiluminescence assay to rapidly measure PRL. Baculovirus expression vectors encoding 16K or 23K hPRL were transfected into insect cells, and PRL secretion verified by Western blotting. Partially purified recombinant 16K hPRL inlbited proliferation of bovine aortic endothelial cells in a dose-dependent manner, while 23K hPRL had no effect. human breast cancer cell line MDA-MB-435 expresses the angiogenic factors vEGF and FGF-2 but not PRL or its receptor. These cells develop tumors and metastases when injected into nude mice. Stable MDA-MB-435 cells that over- express 16K or 23K hPRL have been generated and will be used to determine if 16K hPRL suppresses the growth of breast cancer and metastases in nude mice.
- Medicine and Medical Research