Prolactin overexpression by MDA-MB-435 human breast cancer cells accelerates tumor growth

• Published in: Breast cancer research and treatment Vol. 79; no. 2; pp. 241 - 252
• Main Authors: LIBY, Karen, NELTNER, Bonnie, MOHAMET, Lisa, MENCHEN, Lindsey, BEN-JONATHAN, Nira
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer 01.05.2003; Springer Nature B.V
• Subjects: Animals; Biological and medical sciences; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer research; Cancer therapies; Cell Division; Cells; Feedback, Physiological; Female; Gene Expression Regulation, Neoplastic; Gynecology. Andrology. Obstetrics; Hormones; Humans; Lymphatic Metastasis; Mammary gland diseases; Medical sciences; Mice; Mice, Nude; Neoplasm Transplantation; Prolactin - physiology; Receptors, Prolactin - metabolism; RNA, Messenger - analysis; Tumor Cells, Cultured; Tumors; Cell proliferation; Rodentia; breast cancer; Tumoral marker; Malignant tumor; Gene expression; prolactin receptor; Mammary gland diseases; Protein hormone; Vertebrata; tumors; Mammalia; Adenohypophyseal hormone; Mouse; Prolactin; Animal; Established cell line; Tumor progression; nude mice; Mammary gland; Tumor cell; Hormonal receptor
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1023/A:1023956223037

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.