Prolactin overexpression by MDA-MB-435 human breast cancer cells accelerates tumor growth.
Prolactin (PRL) is an important hormone in mammary tumorigenesis in rodents but its involvement in human breast cancer has been controversial. A role for locally produced PRL in breast carcinogenesis is suggested by its mitogenic action on breast cancer cells and the expression of both PRL and its receptor (PRL-R) in breast carcinomas. Our objective was to examine whether PRL, overexpressed by breast cancer cells, forms an autocrine/paracrine loop that confers a growth advantage for tumors. MDA-MB-435 breast cancer cells overexpressing 23K human PRL were generated, and PRL production and secretion by the clones were confirmed by RT-PCR, western blotting, and the Nb2 bioassay; control clones contain vector only. In vitro the 23K PRL clones proliferated faster and expressed higher levels of the PRL-R protein than controls only when incubated in charcoal-stripped serum (CSS) devoid of lactogenic hormones. When injected into the mammary fatpad of female nude mice or subcutaneously into males, the PRL-overexpressing clones formed tumors that grew 2-4-fold faster than tumors derived from control clones or wild type MDA-MB-435 cells. Western analysis demonstrated significantly higher PRL, PRL-R, and bcl-2 levels in the tumors overexpressing PRL compared to control tumors. These data support a role for breast PRL as a growth/anti-apoptotic factor and suggest that it may serve as a novel therapeutic target for the treatment of breast cancer.
Liby
Karen
K
Department of Cell Biology, University of Cincinnati Medical School, Cincinnati, OH 45267-0521, USA.
Neltner
Bonnie
B
Mohamet
Lisa
L
Menchen
Lindsey
L
Ben-Jonathan
Nira
N
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002455:Cell Division; D025461:Feedback, Physiological; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011388:Prolactin / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D011981:Receptors, Prolactin / Q000378:metabolism; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D011981:Receptors, Prolactin; D011388:Prolactin