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Modulation of the endocytic partners megalin, cubilin, and disabled‐2 by retinoids and steroid hormones in human and mouse mammary epithelial cells
Author(s) -
Rowling Matthew James,
Chlon Timothy M.,
Matthews Donald G.,
Welsh JoEllen
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a349-c
Subject(s) - endocytosis , endocytic cycle , endocrinology , medicine , microbiology and biotechnology , receptor mediated endocytosis , chemistry , receptor , biology
The major circulating form of vitamin D [25‐hydroxyvitamin D 3 , 25(OH)D 3 )] circulates bound to vitamin D‐binding protein (DBP). Prior to activation to 1,25‐dihydroxyvitamin D 3 in the kidney, the 25‐(OH)D 3 ‐DBP complex is internalized via endocytosis, which requires the membrane receptors megalin and cubilin and the adaptor protein disabled‐2 (Dab2). We recently reported that mammary epithelial cells rapidly internalize DBP via endocytosis and are growth inhibited by 25(OH)D 3 . The objective of these studies was to characterize megalin, cubilin, and Dab2 expression in human mammary epithelial cells and murine mammary gland. Using immunoblotting and real‐time PCR, we found that megalin, cubilin, and Dab2 were expressed and dose‐dependently induced by all‐ trans ‐retinoic acid and/or forskolin in T‐47D human breast cancer cells. In addition, immunofluorescence revealed that megalin and Dab2 were expressed on the cell membrane. Similarly, megalin and Dab2 mRNA levels were elevated in mammary epithelia of lactating and β‐estradiol/progesterone‐supplemented mice, animals that exhibit enhanced hormone‐mediated glandular differentiation. These are the first studies to demonstrate that mammary epithelial cells express megalin, cubilin, and Dab2 which is enhanced during differentiation and may explain, at least in part, our finding that mammary cells readily internalize DBP via receptor‐mediated endocytosis. Supported by NIH CA69700, CA103018 to J.W. and Komen Foundation PDF0403052 to M.R.