Establishment and characterisation of human carcinoembryonic antigen transgenic mice

Hasegawa, Takashi; Isobe, Ken‐ichi; Tsuchiya, Yoko; Oikawa, Shinzo; Nakazato, Hiroshi; Ikezawa, Hiroh; Nakashima, Izumi; Shimokata, Kaoru

doi:10.1038/bjc.1991.386

Cited by 20 publications

(6 citation statements)

References 31 publications

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“…The obvious experiment of ablating the GPI and transmembrane genes in mice separately ob viously cannot be done if mice lack the GPIlinked members, and would in any event be complicated by possible functional redundan cy with other adhesion systems. The reverse experiment, that of adding GPI-linked mem bers, such as CEA, to mice by transgenesis, either driven by ubiquitous promoters [40] or the human CEA gene promoter [41], has been done without detectable phenotypic effect. Thus, other than showing that mammals are incredibly tolerant to the addition of genes with potentially disruptive function, the transgenic experiments are not particularly informative.…”

Section: Discussionmentioning

confidence: 99%

Opposite Functions for Two Classes of Genes of the Human Carcinoembryonic Antigen Family

et al. 1995

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The human carcinoembryonic antigen (CEA) family can be divided into two subgroups according to the means of anchorage of member glycoproteins to the cell membrane: glycophos-phatidyl inositol (GPI) linkage and transmembrane linkage. The GPI-linked members tend to be up-regulated in human tumours, whereas the transmembrane-linked members tend to be down-regulated. Thus the question as to whether the GPI members could be formally considered to function as onco-genes and the transmembrane members as tumour suppressors deserves consideration. Members of both subgroups function in vitro as intercellular adhesion molecules, but the characteristics of this adhesion, including temperature and divalent-cation dependence, differ markedly between the groups. Even the mechanism of intermolecular adhesion appears to differ fundamentally in that GPI-linked CEA-CEA binding involves a double reciprocal bonding between two domains, whereas transmembrane-linked biliary glycoprotein (BGP)-BGP binding requires only one domain. Finally, the ectopic expression of CEA in myoblasts can block myogenic differentiation leaving the cells with the ability to divide, while expression of BGP does not affect or may even accelerate myogenic differentiation. These differences in phenotypic effects in vitro thus mirror the differences observed in expression in tumours and support the view that the GPI and transmembrane groups have opposite effects on cells in relation to the malignant phenotype.

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Section: Discussionmentioning

confidence: 99%

Opposite Functions for Two Classes of Genes of the Human Carcinoembryonic Antigen Family

et al. 1995

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“…However, like many other tumor-associated antigens, CEA is a ''self-antigen'' usually expressed during fetal development and later in normal colonic epithelia at low levels. To evaluate vaccines directed against CEA as a self-antigen, a useful animal model was provided by the establishment of mice that carry the transgene for human CEA and express CEA in a tissue-specific manner similar to humans (5)(6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Induction of Mucosal and Systemic Immune Responses against Human Carcinoembryonic Antigen by an Oral Vaccine

et al. 2005

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Carcinoembryonic antigen (CEA) is a tumor-associated antigen targeted for the development of colorectal tumor vaccines. In this study, we developed papillomavirus pseudoviruses encoding the truncated CEA without NH 2 -terminal signal peptide (PV-CEA) as an oral vaccine to induce CEAspecific CTL responses. In CEA transgenic (CEA-Tg) mice orally immunized with PV-CEA, the immunologic tolerance to CEA as a ''self-antigen'' was overcome and both mucosal and systemic CEA-specific cytolytic activities were detected by in vitro 51 Cr release assays. In a tumor prevention model, the growth rate of CEA + tumors was significantly delayed in CEA-Tg mice orally immunized with PV-CEA when compared with the control vaccine. Further, the IFN-; enzyme-linked ImmunoSPOT and in vitro 51 Cr release assay results showed that HLA-A2-restricted, CEA-specific CTL responses were induced in both mucosal and systemic lymphoid tissues in A2 transgenic mice after oral immunization with PV-CEA. Finally, we showed that coadministration of papillomavirus pseudoviruses encoding interleukin-2 with PV-CEA enhanced the generation of A2-restricted, CEA-specific CTLs in aged CEA/A2 double transgenic mice, which were more clinically relevant. Our data suggest that PV-CEA pseudovirus vaccine is a promising oral CEA vaccine for humans to induce CEAspecific CTLs at the site of colorectal tumors (i.e., intestinal mucosa), which might efficiently eliminate CEA + colorectal tumor cells in the mucosa. (Cancer Res 2005; 65(15): 6990-9)

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“…We analysed the thymuses of CEA-transgenic mice established by us (Hasegawa et al, 199 1) and the Kato III tumour cell line. When we used the CEA probe, we could detect CEA mRNA in the transgenic mice's thymuses (data not shown) as mentioned before (Hasegawa et al, 1991) and 4.2, 3.5, and 2.9kb mRNAs in Kato III (Figure 2). However, when we used the NCA probe, we could not detect any mRNA in the CEA-transgenic mice's thymuses or in normal B6 mice's thymuses (Figure 3), but we could detect one band (2.9kb) of mRNA in Kato III ( Figure 3).…”

Section: Resultsmentioning

confidence: 84%

Nonspecific crossreacting antigen (NCA) is a major member of the carcinoembryonic antigen (CEA)-related gene family expressed in lung cancer

1993

Lung Cancer

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Summary Carcinoembryonic antigen (CEA) is one of the most important tumour markers in the management of human carcinoma, including lung cancer. So far, however, because of the nonspecificity of anti-CEA antibodies, it remains unclear whether the experimental measurements of CEA expression really reflect genuine CEA. In normal lung, nonspecific cross reacting antigen (NCA) has been described as a major component of CEA-related antigens. Recently isolated CEA and NCA cDNA clones enabled us to analyse CEA and NCA expression of in vivo tumour specimens and tumour cell lines at mRNA levels. NCA-specific mRNA (but not CEA-specific mRNA) was detected in all normal lung tissues examined. Of 21 lung cancer tissue specimens, nine expressed both NCA and CEA and five expressed only NCA. Of 16 tumour cell lines, two expressed only NCA and one expressed both NCA and CEA, although its level of CEA mRNA was weaker than that of NCA mRNA. Therefore, CEA-related mRNA expression was always accompanied by NCA mRNA expression; there were no cases of CEA mRNA expression alone. These findings suggest that NCA is a major member of the CEA-related gene family expressed in lung cancer.

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Establishment and characterisation of human carcinoembryonic antigen transgenic mice

Cited by 20 publications

References 31 publications

Opposite Functions for Two Classes of Genes of the Human Carcinoembryonic Antigen Family

Opposite Functions for Two Classes of Genes of the Human Carcinoembryonic Antigen Family

Induction of Mucosal and Systemic Immune Responses against Human Carcinoembryonic Antigen by an Oral Vaccine

Nonspecific crossreacting antigen (NCA) is a major member of the carcinoembryonic antigen (CEA)-related gene family expressed in lung cancer

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