Preferential expression of novel MUC1 tumor antigen isoforms in human epithelial tumors and their tumor-potentiating function

International Journal of CancerVolume 71, Issue 5 p. 741-749 Human CancerFree Access Preferential expression of novel MUC1 tumor antigen isoforms in human epithelial tumors and their tumor-potentiating function Amos Baruch, Corresponding Author Amos Baruch Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, IsraelDepartment of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, IsraelSearch for more papers by this authorMor-li Hartmann, Mor-li Hartmann Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, IsraelSearch for more papers by this authorSheila Zrihan-Licht, Sheila Zrihan-Licht Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, IsraelSearch for more papers by this authorShulamit Greenstein, Shulamit Greenstein Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, IsraelSearch for more papers by this authorMatti Burstein, Matti Burstein Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, IsraelSearch for more papers by this authorIafa Keydar, Iafa Keydar Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, IsraelSearch for more papers by this authorMordechai Weiss, Mordechai Weiss Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, IsraelSearch for more papers by this authorNechama Smorodinsky, Nechama Smorodinsky Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, IsraelSearch for more papers by this authorDaniel H. Wreschner, Corresponding Author Daniel H. Wreschner Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, IsraelDepartment of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, IsraelSearch for more papers by this author Amos Baruch, Corresponding Author Amos Baruch Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, IsraelDepartment of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, IsraelSearch for more papers by this authorMor-li Hartmann, Mor-li Hartmann Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, IsraelSearch for more papers by this authorSheila Zrihan-Licht, Sheila Zrihan-Licht Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, IsraelSearch for more papers by this authorShulamit Greenstein, Shulamit Greenstein Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, IsraelSearch for more papers by this authorMatti Burstein, Matti Burstein Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, IsraelSearch for more papers by this authorIafa Keydar, Iafa Keydar Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, IsraelSearch for more papers by this authorMordechai Weiss, Mordechai Weiss Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, IsraelSearch for more papers by this authorNechama Smorodinsky, Nechama Smorodinsky Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, IsraelSearch for more papers by this authorDaniel H. Wreschner, Corresponding Author Daniel H. Wreschner Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, IsraelDepartment of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, IsraelSearch for more papers by this author First published: 06 December 1998 https://doi.org/10.1002/(SICI)1097-0215(19970529)71:5<741::AID-IJC9>3.0.CO;2-RCitations: 68AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Abstract The human MUC1 gene expresses at least 2 type 1 membrane proteins: MUC1/REP, a polymorphic high m.w. MUC1 glycoprotein often highly expressed in breast cancer tissues and containing a variable number of tandem 20 amino acid repeat units, and the MUC1/Y protein, which lacks this repeat array and, therefore, is not polymorphic. Despite their documented importance in signal transduction processes, the relative expression of the 2 isoforms in epithelial tumors is unknown. Using antibody reagents which recognize different MUC1 domains, the expression of these isoforms in malignant epithelial cells has been evaluated. A comparison of the amounts of the 2 isoforms revealed preferential expression of the novel MUC1/Y protein in breast cancer tissue samples. Furthermore, although the MUC1/REP protein is almost undetectable in HeLa cervical adenocarcinoma epithelial cells, the MUC1/Y isoform is extensively expressed in these cells. The presence of the MUC1/Y sequence as well as that of an additional tandem-repeat-array-lacking isoform, designated MUC1/X, were demonstrated by reverse transcriptase PCR amplification of RNA extracted from HeLa and ovarian carcinoma cells. It has been shown previously that the MUC1 cytoplasmic domain interacts with the SH2 domain containing GRB2 protein, which transduces signals to ras, a protein which in its activated form can lead to cell transformation. We present here data demonstrating that MUC1/Y isoform expression increases the tumorigenic potential of DA3 mouse mammary epithelial cells; in contrast, potentiation of tumorigenicity is not observed with MUC1/REP expression. Our studies thus demonstrate that expression of the MUC1 gene in epithelial tumors can give rise to substantial levels of MUC1 proteins devoid of the tandem repeat array, which are generated by alternative splicing mechanisms. Int. J. Cancer 71:741-749, 1997. © 1997 Wiley-Liss Inc. 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