16 K Prolactin as an Angiogenic Inhibitor in Breast Cancer
Annual rept. 1 Jun 2000-31 May 2001
CINCINNATI UNIV OH
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Prolactin PRL is a 23 kDa hormone that targets breast tissue, but its role in breast cancer is controversial. In rodents, PRL promotes spontaneous and carcinogen-induced mammary tumors, while in humans PRL and its receptor are detected in the majority of breast cancer biopsies. We hypothesize that locally produced PRL promotes proliferation andor survival in breast cancer cells, thus providing a growth advantage for a developing tumor. Exogenous PRL 12-2 Co ngml significantly increased MDA-MB-433 cell proliferation by 3 and 5 days. PRL also upregulated PRL-R mRNA as determined by RT-PCR and real time PCR. Wild type cells expressed low levels of both PRL-R and PRL mRNA. MDA cells were transfected with 23K or 16K PRL expression vectors and PRL secretion confirmed by a dot blot assay. Clones overexpressing 23K PRL proliferated faster than vector control cells, while clones overexpressing 16K PRL proliferated slower. Stable clones overexpressing 16K PRL or endostatin will be used to determine if 16K hPRL suppresses the growth of breast cancer and metastases in nude mice. Clones overexpressing 23K PRL will be used to determine if PRL is mitogenic and provides a growth advantage for tumors.
- Medicine and Medical Research