Open AccessCEACAM 1 long isoform has opposite effects on the growth of human mastocytosis and medullary thyroid carcinoma cells
Author(s) -
Ueshima Chiyuki,
Kataoka Tatsuki R.,
Takei Yusuke,
Hirata Masahiro,
Sugimoto Akihiko,
Hirokawa Mitsuyoshi,
Okayama Yoshimichi,
Blumberg Richard S.,
Haga Hironori
Publication year - 2017
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1050
Subject(s) - proto oncogene tyrosine protein kinase src , biology , tyrosine kinase , gene isoform , cancer research , protein tyrosine phosphatase , microbiology and biotechnology , kinase , signal transduction , gene , biochemistry
Carcinoembryonic antigen‐related cell adhesion molecule 1 ( CEACAM 1) is expressed in a number of tumor cell types. The immunoreceptor tyrosine‐based inhibitory motif ( ITIM )‐containing isoforms of this molecule which possess a long cytoplasmic tail ( CEACAM 1‐L) generally play inhibitory roles in cell function by interacting with Src homology 2 domain‐containing tyrosine phosphatase ( SHP )‐1 and/or SHP ‐2. Src family kinases ( SFK s) are also known to bind to and phosphorylate CEACAM 1‐L isoforms. Here, we report that CEACAM 1 was uniquely expressed at high levels in both human neoplastic mast cells (mastocytosis) and medullary thyroid carcinoma cell ( MTC ) lines, when compared with their expression in nonneoplastic mast cells or nonneoplastic C cells. This expression was mainly derived from CEACAM 1‐L isoforms based upon assessment of CEACAM 1 mRNA expression. CEACAM 1 knockdown upregulated cell growth of HMC 1.2 cells harboring KIT mutations detected in clinical mastocytosis, whereas downregulated the growth of TT cells harboring RET mutations detected in clinical MTC s. Immunoblotting, ELISA and immunoprecipitaion analysis showed that activated SHP ‐1 is preferentially associated with CEACAM 1 in HMC 1.2 cells harboring KIT mutations, whereas Src family kinases ( SFK s) are preferentially associated with CEACAM 1 in TT cells harboring RET mutations. These studies suggest that the dominantly interacting proteins SHP 1 or SFK determine whether CEACAM 1‐L displays a positive or negative role in tumor cells.