Lactoferrin: A Tamoxifen-Responsive Protein in Normal and Malignant Human Endometrial Cells in Culture

• Published in: Experimental and molecular pathology 2001-04, Vol.70 (2), p.71-76
• Main Authors: Albright, Craig D., Kaufman, David G.
• Format: Article
• Language: English
• Subjects: Animals; Anticarcinogenic Agents - pharmacology; Antineoplastic agents; Biological and medical sciences; Blotting, Western; Cell Division - drug effects; Cell Survival - drug effects; Cells, Cultured; Chemotherapy; Drug Resistance; Endometrial Neoplasms - metabolism; Endometrial Neoplasms - pathology; Endometrium - cytology; Endometrium - drug effects; Enzyme Inhibitors - pharmacology; Female; Humans; Lactoferrin - drug effects; Lactoferrin - immunology; Lactoferrin - physiology; Medical sciences; Microscopy, Confocal; Neutralization Tests; Pharmacology. Drug treatments; Protein Kinase C - metabolism; Rabbits; Staurosporine - pharmacology; Tamoxifen - pharmacology; Tumor Cells, Cultured
• ISSN: 0014-4800; 1096-0945
• DOI: 10.1006/exmp.2000.2354

We investigated the possible role of the estrogen-regulated protein lactoferrin (Lf) in the response of isolated normal human endometrial epithelial cells (NHEC) and established human endometrial carcinoma (EC) cell lines to tamoxifen (TAM). Using confocal laser scanning microscopy and a monospecific antibody, Lf was localized to the cytoplasm of normal and EC cells. Antibody neutralization of secreted Lf inhibited, whereas exogenous Lf (0–100 μg/ml) enhanced, cell proliferation in both classes of cells. Treatment of NHEC with TAM inhibited cell growth via a protein kinase-C-mediated pathway, concomitant with a reduction in the staining intensity for Lf. Importantly, in EC cells, TAM greatly enhanced the staining intensity for Lf, but did not affect cell growth. We propose that stable expression of Lf protein by EC cells may impart a survival advantage to these cells, which may, in part, account for the resistance of these cells to tamoxifen.