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The immunoreceptor tyrosine\u2010based inhibitory motif (ITIM<\/jats:styled-content>)\u2010containing isoforms of this molecule which possess a long cytoplasmic tail (CEACAM<\/jats:styled-content>1\u2010L) generally play inhibitory roles in cell function by interacting with Src homology 2 domain\u2010containing tyrosine phosphatase (SHP<\/jats:styled-content>)\u20101 and\/or SHP<\/jats:styled-content>\u20102. Src family kinases (SFK<\/jats:styled-content>s) are also known to bind to and phosphorylate CEACAM<\/jats:styled-content>1\u2010L isoforms. Here, we report that CEACAM<\/jats:styled-content>1 was uniquely expressed at high levels in both human neoplastic mast cells (mastocytosis) and medullary thyroid carcinoma cell (MTC<\/jats:styled-content>) lines, when compared with their expression in nonneoplastic mast cells or nonneoplastic C cells. This expression was mainly derived from CEACAM<\/jats:styled-content>1\u2010L isoforms based upon assessment of CEACAM<\/jats:styled-content>1 mRNA<\/jats:styled-content> expression. CEACAM<\/jats:styled-content>1 knockdown upregulated cell growth of HMC<\/jats:styled-content>1.2 cells harboring KIT<\/jats:styled-content> mutations detected in clinical mastocytosis, whereas downregulated the growth of TT<\/jats:styled-content> cells harboring RET<\/jats:styled-content> mutations detected in clinical MTC<\/jats:styled-content>s. Immunoblotting, ELISA<\/jats:styled-content> and immunoprecipitaion analysis showed that activated SHP<\/jats:styled-content>\u20101 is preferentially associated with CEACAM<\/jats:styled-content>1 in HMC<\/jats:styled-content>1.2 cells harboring KIT<\/jats:styled-content> mutations, whereas Src family kinases (SFK<\/jats:styled-content>s) are preferentially associated with CEACAM<\/jats:styled-content>1 in TT<\/jats:styled-content> cells harboring RET<\/jats:styled-content> mutations. These studies suggest that the dominantly interacting proteins SHP<\/jats:styled-content>1 or SFK<\/jats:styled-content> determine whether CEACAM<\/jats:styled-content>1\u2010L displays a positive or negative role in tumor cells.<\/jats:p>","DOI":"10.1002\/cam4.1050","type":"journal-article","created":{"date-parts":[[2017,3,24]],"date-time":"2017-03-24T04:51:35Z","timestamp":1490331095000},"page":"845-856","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["CEACAM<\/scp>1 long isoform has opposite effects on the growth of human mastocytosis and medullary thyroid carcinoma cells"],"prefix":"10.1002","volume":"6","author":[{"given":"Chiyuki","family":"Ueshima","sequence":"first","affiliation":[{"name":"Department of Diagnostic Pathology Kyoto University Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3095-8976","authenticated-orcid":false,"given":"Tatsuki R.","family":"Kataoka","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology Kyoto University Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Takei","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology Kyoto University Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Hirata","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology Kyoto University Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Sugimoto","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology Kyoto University Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuyoshi","family":"Hirokawa","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology Kuma Hospital Hyogo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshimichi","family":"Okayama","sequence":"additional","affiliation":[{"name":"Division of Molecular Cell Immunology and Allergology Advanced Medical Research Center Nihon University Graduate School of Medical Science Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard S.","family":"Blumberg","sequence":"additional","affiliation":[{"name":"Gastroenterology Division Department of Medicine Brigham and Women's Hospital Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironori","family":"Haga","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology Kyoto University Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,3,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1864"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.13.2.1273"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.5.1469"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13848"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.1.335"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(97)80079-9"},{"key":"e_1_2_7_8_1","first-page":"1236","article-title":"The tumor growth\u2010inhibiting cell adhesion molecule CEACAM1 (C\u2010CAM) is differently expressed in proliferating and quiescent epithelial cells and regulates cell proliferation","volume":"60","author":"Singer B. 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