
Characterization and Molecular Cloning of a Novel MUC1 Protein, Devoid of Tandem Repeats, Expressed in Human Breast Cancer Tissue
Author(s) -
ZrihanLicht Sheila,
Vos Hans, L.,
Baruch Amos,
ElroyStein Orna,
Sagiv Dalit,
Keydar Iafa,
Hilkens John,
Wreschner Daniel H.
Publication year - 1994
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1994.00787.x
Subject(s) - tandem repeat , biology , complementary dna , muc1 , alternative splicing , rna splicing , microbiology and biotechnology , transmembrane protein , molecular cloning , transmembrane domain , variable number tandem repeat , genetics , gene , messenger rna , cancer , genome , rna , allele , receptor
The human breast cancer marker protein, MUC1, is a polymorphic transmembrane molecule containing a large extracellular domain that is primarily composed of a variable number of highly conserved 20‐amino‐acid tandem repeats. We report here the detection of a novel invariantly sized 1.2‐kb MUC1 mRNA, in addition to the large polymorphic mRNAs, by probing Northern blots with MUC1‐cDNA‐unique‐sequence probes. The nucleotide sequence of this novel MUC1 mRNA demonstrates that it is identical to the MUC1 cDNA sequences downstream and upstream to the tandem‐repeat array of the transmembrane form of MUC1. However, it contains neither the central tandem repeat array itself nor its directly flanking sequences that are deleted by a differential splicing event utilizing splice acceptor and donor sequences 5′ and 3′ to the tandem‐repeat array. The splice event retains, downstream to the splice acceptor site, an open reading frame identical to that of the repeat‐array‐containing MUC1 thereby generating the novel MUC1/Y protein. Cells transiently transfected with the novel MUC1/Y cDNA express the MUC1/Y protein that is modified by glycosylation. The MUC1/Y protein is also readily detected in human breast cancer cells grown in vitro. Furthermore, primary breast cancer tissue samples demonstrate significant levels of the MUC1/Y protein whereas expression in tissue adjacent to the tumor is undetectable. Molecular characterization presented here, of the novel MUC1/Y molecule lacking the repeat array, suggests that it is likely to play a role distinct to that of the polymorphic repeat‐array‐positive MUC1 protein and that it may act as a new marker protein for human breast cancer.