Breast 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 Mr-40,000 receptor-associated protein.
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, Mr-40,000 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 Mr 105,000 and Mr 130,000, 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, 20,855-20,869]. 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.
Martensen
P M
PM
Department of Molecular and Structural Biology, University of Aarhus, Denmark.
Oka
K
K
Christensen
L
L
Rettenberger
P M
PM
Petersen
H H
HH
Christensen
A
A
Chan
L
L
Heegaard
C W
CW
Andreasen
P A
PA
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001943:Breast Neoplasms / Q000378:metabolism*; D002236:Carbohydrate Conformation; D002277:Carcinoma / Q000378:metabolism*; D004705:Endocytosis; D004848:Epithelium; D005091:Exons; D006031:Glycosylation; D006801:Humans; D007150:Immunohistochemistry; D015674:Mammary Neoplasms, Animal / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D011817:Rabbits; D011973:Receptors, LDL / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism*; D015843:Serpins / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D008565:Membrane Proteins; D011973:Receptors, LDL; D015843:Serpins; C036053:VLDL receptor; D012697:Serine Endopeptidases