Open AccessBreast Carcinoma Epithelial Cells Express a Very Low‐Density Lipoprotein Receptor Variant Lacking the O‐Linked Glycosylation Domain Encoded by Exon 16, But with Full Binding Activity for Serine Proteinase/Serpin Complexes and M r ‐40000 Receptor‐Associated Protein
Author(s) -
Martensen Pia M.,
Oka Kazuhiro,
Christensen Lise,
Rettenberger Peter M.,
Petersen Helle H.,
Christensen Anni,
Chan Lawrence,
Heegaard Christian W.,
Andreasen Peter A.
Publication year - 1997
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1997.00583.x
Subject(s) - serpin , exon , glycosylation , serine , chemistry , ldl receptor , serine protease , gene , cancer research , microbiology and biotechnology , lipoprotein , biochemistry , biology , phosphorylation , enzyme , cholesterol , protease
Very‐low density lipoprotein receptor (VLDLR) belongs to the low‐density lipoprotein receptor family of endocytosis receptors. It binds a variety of different ligands, including apolipoprotein E, M r ‐40000 receptor‐associated‐protein (RAP), and some serine proteinase/serpin complexes. We previously demonstrated the occurrence of two forms of VLDLR in SDS/PAGE, migrating with M r 105000 and M r 130000, respectively [Heegaard, C. W., Simonsen, A. C. W., Oka, K., Kjøller, L., Christensen, A., Madsen, B., Ellgaard, L., Chan, L. & Andreasen, P. A. (1995) J. Biol. Chem. 270 , 20855–20869]. We now demonstrate that these two forms correspond to forms with the absence (type‐II) and presence (type‐I) of the O‐linked glycosylation domain encoded by exon 16, respectively. We show that the two forms have the same binding affinity to RAP and serine proteinase/serpin complexes. Using reverse transcription and PCR, we demonstrate that the splice variation giving rise to the two forms is highly cell specific. In particular, we demonstrate that human breast carcinomas express predominantly or exclusively the variant lacking exon 16. By immunohistochemistry, we demonstrate that VLDLR is mainly expressed by the epithelial cancer cells in these carcinomas. The VLDLR variant expressed by epithelial cancer cells could function in the clearance of cell‐surface‐associated serine proteinase/serpin complexes in breast carcinomas.