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. 2001 Apr 15;355(Pt 2):417–423. doi: 10.1042/0264-6021:3550417

Differences in tissue-specific and embryonic expression of mouse Ceacam1 and Ceacam2 genes.

E Han 1, D Phan 1, P Lo 1, M N Poy 1, R Behringer 1, S M Najjar 1, S H Lin 1
PMCID: PMC1221753  PMID: 11284729

Abstract

The intercellular adhesion molecule CEACAM1, also known as C-CAM1 (where CAM is cell-adhesion molecule), can function as a tumour suppressor in several carcinomas, including those of the prostate, breast, bladder and colon. This suggests that CEACAM1 may play an important role in the regulation of normal cell growth and differentiation. However, there is no direct evidence to support this putative function of CEACAM1. To elucidate its physiological function by targeted gene deletion, we isolated the Ceacam genes from a mouse 129 Sv/Ev library. Although there is only one Ceacam1 gene in humans and one in rats, two homologous genes (Ceacam1 and Ceacam2) have been identified in the mouse. Our sequence analysis revealed that the genes encoded nine exons and spanned approx. 16-17 kb (Ceacam1) and 25 kb (Ceacam2). The genes were highly similar (79.6%). The major differences in the protein-coding regions were located in exons 2, 5 and 6 (76.9%, 87.0% and 78.5% similarity respectively). In addition, introns 2, 5 and 7 were also significantly different, being 29.7%, 59.8% and 64.5% similar respectively. While most of these differences were due to nucleotide substitutions, two insertions of 418 and 5849 bp occurred in intron 2 of Ceacam2, and another two insertions of 1384 and 197 bp occurred in introns 5 and 7 respectively. To determine whether functional redundancy exists between Ceacam1 and Ceacam2, we examined their expression in 16 mouse tissues by using semi-quantitative reverse transcription-PCR. As in human and rat, in the mouse Ceacam1 mRNA was highly abundant in the liver, small intestine, prostate and spleen. In contrast, Ceacam2 mRNA was only detected in kidney, testis and, to a lesser extent, spleen. Reverse transcription-PCR using testis RNA indicated that Ceacam2 in the testis is an alternatively spliced form containing only exons 1, 2, 5, 6, 8 and 9. In the mouse embryo, Ceacam1 mRNA was detected at day 8.5, disappeared between days 9.5 and 12.5, and re-appeared at day 19. On the other hand, no Ceacam2 mRNA was detected throughout embryonic development. The different tissue expression patterns and regulation during embryonic development suggest that the CEACAM1 and CEACAM2 proteins, although highly similar, may have different functions both during mouse development and in adulthood.

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Selected References

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  1. Bamberger A. M., Riethdorf L., Nollau P., Naumann M., Erdmann I., Götze J., Brümmer J., Schulte H. M., Wagener C., Löning T. Dysregulated expression of CD66a (BGP, C-CAM), an adhesion molecule of the CEA family, in endometrial cancer. Am J Pathol. 1998 Jun;152(6):1401–1406. [PMC free article] [PubMed] [Google Scholar]
  2. Beauchemin N., Draber P., Dveksler G., Gold P., Gray-Owen S., Grunert F., Hammarström S., Holmes K. V., Karlsson A., Kuroki M. Redefined nomenclature for members of the carcinoembryonic antigen family. Exp Cell Res. 1999 Nov 1;252(2):243–249. doi: 10.1006/excr.1999.4610. [DOI] [PubMed] [Google Scholar]
  3. Brandriff B. F., Gordon L. A., Tynan K. T., Olsen A. S., Mohrenweiser H. W., Fertitta A., Carrano A. V., Trask B. J. Order and genomic distances among members of the carcinoembryonic antigen (CEA) gene family determined by fluorescence in situ hybridization. Genomics. 1992 Apr;12(4):773–779. doi: 10.1016/0888-7543(92)90308-f. [DOI] [PubMed] [Google Scholar]
  4. Cheung P. H., Culic O., Qiu Y., Earley K., Thompson N., Hixson D. C., Lin S. H. The cytoplasmic domain of C-CAM is required for C-CAM-mediated adhesion function: studies of a C-CAM transcript containing an unspliced intron. Biochem J. 1993 Oct 15;295(Pt 2):427–435. doi: 10.1042/bj2950427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cheung P. H., Thompson N. L., Earley K., Culic O., Hixson D., Lin S. H. Cell-CAM105 isoforms with different adhesion functions are coexpressed in adult rat tissues and during liver development. J Biol Chem. 1993 Mar 25;268(9):6139–6146. [PubMed] [Google Scholar]
  6. Estrera V. T., Luo W., Phan D., Earley K., Hixson D. C., Lin S. H. The cytoplasmic domain of C-CAM1 tumor suppressor is necessary and sufficient for suppressing the tumorigenicity of prostate cancer cells. Biochem Biophys Res Commun. 1999 Oct 5;263(3):797–803. doi: 10.1006/bbrc.1999.1443. [DOI] [PubMed] [Google Scholar]
  7. Hinoda Y., Neumaier M., Hefta S. A., Drzeniek Z., Wagener C., Shively L., Hefta L. J., Shively J. E., Paxton R. J. Molecular cloning of a cDNA coding biliary glycoprotein I: primary structure of a glycoprotein immunologically crossreactive with carcinoembryonic antigen. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6959–6963. doi: 10.1073/pnas.85.18.6959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hsieh J. T., Luo W., Song W., Wang Y., Kleinerman D. I., Van N. T., Lin S. H. Tumor suppressive role of an androgen-regulated epithelial cell adhesion molecule (C-CAM) in prostate carcinoma cell revealed by sense and antisense approaches. Cancer Res. 1995 Jan 1;55(1):190–197. [PubMed] [Google Scholar]
  9. Kleinerman D. I., Dinney C. P., Zhang W. W., Lin S. H., Van N. T., Hsieh J. T. Suppression of human bladder cancer growth by increased expression of C-CAM1 gene in an orthotopic model. Cancer Res. 1996 Aug 1;56(15):3431–3435. [PubMed] [Google Scholar]
  10. Kleinerman D. I., Troncoso P., Lin S. H., Pisters L. L., Sherwood E. R., Brooks T., von Eschenbach A. C., Hsieh J. T. Consistent expression of an epithelial cell adhesion molecule (C-CAM) during human prostate development and loss of expression in prostate cancer: implication as a tumor suppressor. Cancer Res. 1995 Mar 15;55(6):1215–1220. [PubMed] [Google Scholar]
  11. Kunath T., Ordoñez-Garcia C., Turbide C., Beauchemin N. Inhibition of colonic tumor cell growth by biliary glycoprotein. Oncogene. 1995 Dec 7;11(11):2375–2382. [PubMed] [Google Scholar]
  12. Lin S. H., Culic O., Flanagan D., Hixson D. C. Immunochemical characterization of two isoforms of rat liver ecto-ATPase that show an immunological and structural identity with a glycoprotein cell-adhesion molecule with Mr 105,000. Biochem J. 1991 Aug 15;278(Pt 1):155–161. doi: 10.1042/bj2780155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Luo W., Wood C. G., Earley K., Hung M. C., Lin S. H. Suppression of tumorigenicity of breast cancer cells by an epithelial cell adhesion molecule (C-CAM1): the adhesion and growth suppression are mediated by different domains. Oncogene. 1997 Apr 10;14(14):1697–1704. doi: 10.1038/sj.onc.1200999. [DOI] [PubMed] [Google Scholar]
  14. Najjar S. M., Boisclair Y. R., Nabih Z. T., Philippe N., Imai Y., Suzuki Y., Suh D. S., Ooi G. T. Cloning and characterization of a functional promoter of the rat pp120 gene, encoding a substrate of the insulin receptor tyrosine kinase. J Biol Chem. 1996 Apr 12;271(15):8809–8817. doi: 10.1074/jbc.271.15.8809. [DOI] [PubMed] [Google Scholar]
  15. Neumaier M., Paululat S., Chan A., Matthaes P., Wagener C. Biliary glycoprotein, a potential human cell adhesion molecule, is down-regulated in colorectal carcinomas. Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10744–10748. doi: 10.1073/pnas.90.22.10744. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Nollau P., Scheller H., Kona-Horstmann M., Rohde S., Hagenmüller F., Wagener C., Neumaier M. Expression of CD66a (human C-CAM) and other members of the carcinoembryonic antigen gene family of adhesion molecules in human colorectal adenomas. Cancer Res. 1997 Jun 15;57(12):2354–2357. [PubMed] [Google Scholar]
  17. Nédellec P., Dveksler G. S., Daniels E., Turbide C., Chow B., Basile A. A., Holmes K. V., Beauchemin N. Bgp2, a new member of the carcinoembryonic antigen-related gene family, encodes an alternative receptor for mouse hepatitis viruses. J Virol. 1994 Jul;68(7):4525–4537. doi: 10.1128/jvi.68.7.4525-4537.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Nédellec P., Turbide C., Beauchemin N. Characterization and transcriptional activity of the mouse biliary glycoprotein 1 gene, a carcinoembryonic antigen-related gene. Eur J Biochem. 1995 Jul 1;231(1):104–114. doi: 10.1111/j.1432-1033.1995.tb20676.x. [DOI] [PubMed] [Google Scholar]
  19. Odin P., Asplund M., Busch C., Obrink B. Immunohistochemical localization of cellCAM 105 in rat tissues: appearance in epithelia, platelets, and granulocytes. J Histochem Cytochem. 1988 Jul;36(7):729–739. doi: 10.1177/36.7.3290331. [DOI] [PubMed] [Google Scholar]
  20. Prall F., Nollau P., Neumaier M., Haubeck H. D., Drzeniek Z., Helmchen U., Löning T., Wagener C. CD66a (BGP), an adhesion molecule of the carcinoembryonic antigen family, is expressed in epithelium, endothelium, and myeloid cells in a wide range of normal human tissues. J Histochem Cytochem. 1996 Jan;44(1):35–41. doi: 10.1177/44.1.8543780. [DOI] [PubMed] [Google Scholar]
  21. Pu Y. S., Luo W., Lu H. H., Greenberg N. M., Lin S. H., Gingrich J. R. Differential expression of C-CAM cell adhesion molecule in prostate carcinogenesis in a transgenic mouse model. J Urol. 1999 Sep;162(3 Pt 1):892–896. doi: 10.1097/00005392-199909010-00085. [DOI] [PubMed] [Google Scholar]
  22. Rosenberg M., Nédellec P., Jothy S., Fleiszer D., Turbide C., Beauchemin N. The expression of mouse biliary glycoprotein, a carcinoembryonic antigen-related gene, is down-regulated in malignant mouse tissues. Cancer Res. 1993 Oct 15;53(20):4938–4945. [PubMed] [Google Scholar]
  23. Senapathy P., Shapiro M. B., Harris N. L. Splice junctions, branch point sites, and exons: sequence statistics, identification, and applications to genome project. Methods Enzymol. 1990;183:252–278. doi: 10.1016/0076-6879(90)83018-5. [DOI] [PubMed] [Google Scholar]
  24. Thompson J. A., Grunert F., Zimmermann W. Carcinoembryonic antigen gene family: molecular biology and clinical perspectives. J Clin Lab Anal. 1991;5(5):344–366. doi: 10.1002/jcla.1860050510. [DOI] [PubMed] [Google Scholar]
  25. Thompson N. L., Lin S. H., Panzica M. A., Hixson D. C. Cell CAM 105 isoform RNA expression is differentially regulated during rat liver regeneration and carcinogenesis. Pathobiology. 1994;62(4):209–220. doi: 10.1159/000163912. [DOI] [PubMed] [Google Scholar]
  26. Williams R. K., Jiang G. S., Holmes K. V. Receptor for mouse hepatitis virus is a member of the carcinoembryonic antigen family of glycoproteins. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5533–5536. doi: 10.1073/pnas.88.13.5533. [DOI] [PMC free article] [PubMed] [Google Scholar]

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