Analysis of the Secreted Novel Breast-Cancer-Associated MUC1/Zs Cytokine
Abstract
As described in our research proposal the MUC1 gene is expressed in secretory epithelial tissues and at exceptionally high levels in human breast cancer cells. It is a well-known and widely accepted marker for breast cancer that can generate several functionally distinct MUC1 protein isoforms some containing a 20 amino acid tandem-repeat-array and additional forms lacking this domain. Findings emanating originally from our laboratory and subsequently confirmed by others, implicate the participation of the MUC1 proteins in signaling pathways. Analysis of MUC1 1 RT-PCR cDNA products revealed a supplementary and unique splice variant, MUC1/Zs, which is devoid of the tandem repeat array and utilizes a perfect out-of- frame splice acceptor site downstream to the tandem repeats. This splice event generates a secreted MUC1/Zs protein that harbors an N-terminal signal peptide and which contains a unique C-terminal stretch of 43 amino acids- this region shows marked homology with restricted regions of known cytokines and chemokines. We proposed to investigate the hypothesis that the MUCl/Zs protein is a novel, biologically important, cytokine by (a) analyzing MUC1/Zs protein expression in tumor tissues and correlating this expression with that of other MUC1 1 isoforms, (b) characterizing the signaling function of MUC1 1 /Zs and proteins (receptor molecules?) with which the MUC1/Zs protein interacts, and (c) studying, both in-vivo and in in-vitro, the effect on tumor cell growth mediated by the MUC1/Zs protein.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2001
- Accession Number
- ADA396834
Entities
People
- Daniel H. Wreschner
Organizations
- Tel Aviv University