• 제목, 요약, 키워드: Cancer-testis antigen

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Cancer-testis (CT) 유전자의 고찰 (Review of Cancer-Testis (CT) Genes)

  • 김미희;송명하;이상률
    • 생명과학회지
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    • v.21 no.6
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    • pp.912-922
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    • 2011
  • Cancer-testis (CT) antigen은 다양한 종양과 정상 고환에서 제한적으로 발현되고, 암환자에서 체액성 면역과 세포성 면역반응을 일으키는 종양항원이다. 지금까지 MAGE, NY-ESO-1, GAGE, BAGE, LAGE, SSX2, NY-SAR-35를 포함하여 100개 이상의 CT antigen들이 동정되었고, 이러한 CT antigen들은 백신을 이용한 면역치료에 있어서 중요한 요소로 작용할 것으로 사료된다. CT antigen은 여러 가지 방법들을 통해 확인할 수 있고, X 염색체에 암호화 되어있는 CT-X gene과 X 염색체에 암호화 되어있지 않은 non-X CT gene으로 나눌 수 있다. 또한 몇몇의 종양에서 비정상적으로 활성화되지 않거나 발현되지 않는 CT antigen도 존재한다. 생식세포 조직과 종양에서 CT-X gene의 생물학적 역할이 아직 명확하게 규명되지 않았지만, 현재 여러 종류의 CT antigen을 이용한 암백신 치료법이 시도되고 있다. 본 논문은 암의 면역치료를 위한 CT antigen의 최근 연구동향과 앞으로의 연구방향에 대해 서술하고자 한다.

한국 유방암 환자에서 cancer/testis antigen의 발현분석 (A comprehensive Analysis of a Large Panel of Cancer/Testis (CT) Antigens in Korea Breast Cancer)

  • 배재호;김민주;박해림;송명하;김지연;이창훈;곽희숙;이상률
    • 생명과학회지
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    • v.19 no.7
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    • pp.886-891
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    • 2009
  • Cancer/testis(CT) antigens은 여러 종료의 암에서는 발현이 되지만, 정상조직에서는 고환에서만 발현이 되는 특이성을 가지고 있다. 이러한 특이성은 immunotherapy을 하기 위한 항암백신 개발에 매력적인 유전자로 알려져 있다. 본 연구에서는 29개의 한국유방암조직에서 13개의 CT antigens (NY-SAR35, SCP-1, SSX-1, SSX-2, SSX-4, MAGE-1, MAGE-3, MAGE-4, MAGE-10, CT-7, NY-TLU57, NY-ESO-1, and LAGE-1)의 발현빈도를 RT-PCR을 통하여 조사하고 환자의 임상학적 분류와 CT antigens의 발현빈도에 대하여 조사하였다. 29개의 유방암조직에 RT-PCR결과, 13개의 CT antigen중에 MAGE-3 (66%)와 MAGE-1(57%)에서 발현빈도가 가장 높았고 LAGE-1 (55%),NY-SAR-35 (49%),MAGE-4(41%), NY-ESO-1(38%), CT-7(24%), SSX-4(24%)순으로 발현빈도를 보였다. 그러나 SSX-1, SSX-2. MAGE-10와 NY-TLU-57의 발현은 3-7%로 매우 낮았고 특히 SCP-1는 발현되지 않았다. 29 유방암 조직에서 적어도 하나 이상의 CT antigen이 발현되는 샘플은 28(98%)이였다. 그러나 환자의 임상학적 분류와 CT antigens의 발현빈도와는 특징적인 관꼐가 없음을 알수있었다. 29개의 유방암조직에서 MAGE-3와 NY-ESO-1의 Protein level에서의 발현을 알아보기 위하여monoclonal antibody를 이용하여 면역조직염색을 하였다. MAGE-3은 29개 조직중에서 12개의 조직에서 발현되었으며 NY-ESO-1은 11개의 조직에서 발현되었다. 그러므로 CT antigens은 한국 유방암 조직에서 빈번하게 발현된 것을 알 수 있었으며 CT antigens을 기반으로 한 암 백신개발의 잠재적인 표적이 될 수 있을 것이라 사료된다.

Role of CAGE, a Novel Cancer/Testis Antigen, in Various Cellular Processes, Including Tumorigenesis, Cytolytic T Lymphocyte Induction, and Cell Motility

  • Kim, Young-Mi;Jeoung, Doo-Il
    • Journal of Microbiology and Biotechnology
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    • v.18 no.3
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    • pp.600-610
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    • 2008
  • A cancer-associated antigen gene (CAGE) was identified by serological analysis of a recombinant cDNA expression library (SEREX). The gene was identified by screening cDNA expression libraries of human testis and gastric cancer cell lines with sera from patients with gastric cancer. CAGE was found to contain a D-E-A-D box domain and encodes a putative protein of 630 amino acids with possible helicase activity. The CAGE gene is widely expressed in various cancer tissues and cancer cell lines. Demethylation plays a role in the activation of CAGE in certain cancer cell lines where the gene is not expressed. The functional roles of CAGE in tumorigenesis, the molecular mechanisms of CAGE expression, and cell motility are also discussed.

Ectopic Overexpression of Coiled-Coil Domain Containing 110 Delays G2/M Entry in U2-OS Cells

  • Lee, Sue Nyoung;Hong, Kyeong-Man;Seong, Yeon Sun;Kwak, Sahng-June
    • 한국발생생물학회지:발생과생식
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    • v.24 no.2
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    • pp.101-111
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    • 2020
  • Coiled-coil domain containing 110 (CCDC110, KM-HN-1) is a protein containing C-terminal coiled-coil domain (CCD) which was previously discovered as a member of the human cancer/testis antigen (CTA). In addition, CCDC110 has both nuclear localization signal sequence and the leucine zipper motif. Although the functional role of CCDC110 has yet to be fully identified, the mRNA expression levels of CCDC110 are known to be highly elevated in various cancer types including testis, implying its relevance to cancer pathogenesis. In this study, we first developed several monoclonal antibody (mAb) hybridoma clones targeting CCDC110 and further isolated clone by characterizing for its specificity using immunoblotting and immunoprecipitation approaches with basal parenchymal sperm cells in testis tissue. Next, using these mAbs, we showed that the Tet-inducible overexpression of CCDC110 protein delayed the entry of G2/M phase in U2-OS osteosarcoma cells. Based on these results, we propose that CCDC110 plays a crucial role in cell cycle progression.

폐암 환자에서 면역항원유전자의 혈청학적 동정 (Identification of Tumor Antigens in Lung Cancer Patient by SEREX)

  • 민영기;하진목;손영옥;박해림;이민기;박영민;김철민;이상률
    • 생명과학회지
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    • v.17 no.8
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    • pp.1082-1089
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    • 2007
  • 혈청학적 유전자 검색 방법(SEREX)은 암 환자의 면역계를 인식하는 종양 면역유전체(Cancer Immunome)를 형성하는 수많은 종양항원의 발견을 이끌어왔다. 본 연구는 정상인의 고환 조직으로 만들어진 cDNA liabary을 사용하여 폐암환자의 혈청으로부터 40개의 종양항원을 동정하여 그 항원들을 KP-LuT-1부터 KP-LuT-40까지 명명하였다. 이들 항원 중에서 20개는 기존의 다른 종류의 암에서 분리된 것이며 20개는 본 실험에서 새롭게 동정 된 항원들이었다. 유전자 분석을 통하여 분리된 26개의 항원들은 그 단백질의 기능이 알려진 것이었고 14개의 항원들은 기능이 분석되지 않은 유전체의 산물이었다. 이들 항원 중에서 hypothetic단백질 KP-LuT-6는 정상조직에서 제한적으로 발현되었다. RT-PCR에 의한 발현분석 결과에서 16개의 정상조직 중 고환에서만 강력하게 발현 하였고 다른 조직에서는 발현되지 않으나 폐암(3/10), 위암 (3/10) 과 유방암(1/5)들에서 발현 하였다. 이 결과는 KP-LuT-6의 항원이 암 면역치료를 위한 잠재적 유전자로 사용될 수 있는 Cancer/Testis(CT) 항원과 비슷한 유전 자로 사료된다.

Identification and characterization of a novel cancer/testis antigen gene

  • Cho , Bom-Soo;Lee, Dae-Yeon;Lim , Yoon;Park, Sae-Young;Lee, Ho-Soon;Kim, Woo-Ho;Yang, Han-Kwang;Bang, Yung-Jue;Jeoung , Doo-Il
    • 대한약학회:학술대회논문집
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    • pp.326.1-326
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    • 2002
  • We applied serological analysis of cDNA expression library technique to identify cancer-associated genes. We screened cDNA expression libraries of human testis and gastric cancer cell lines with sera of patients with gastric cancers. We identified a gene whose expression is testis-specific among normal tissues. We cloned and characterized this novel gene. It contains D-E-A-D box domain and encodes a putative protein of 630 amino acids with possible helicase activity. It showed wide expression in various cancer tissues and cancer cell lines. (omitted)

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Are So-Called Cancer-Testis Genes Expressed Only in Testis?

  • Ghafouri-Fard, Soudeh;Rezazadeh, Fatemeh;Zare-Abdollahi, Davood;Omrani, Mir Davood;Movafagh, Abolfazl
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.18
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    • pp.7703-7705
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    • 2014
  • Cancer-testis (CT) antigens are a group of tumor-associated antigens with restricted expression in normal tissues except for testis and expression in a wide variety of tumor tissues. This pattern of expression makes them suitable targets for immunotherapy as well as potential biomarkers for early detection of cancer. However, some genes attributed to this family are now known to be expressed in other normal tissues which put their potential applications in immunotherapy and cancer detection under question. Here we analyzed expression of two previously known CT antigens, RHOXF2 and PIWIL2, in AML patients versus normal donors and found no significant difference in the expression of these genes between the two groups. As these two genes showed expression in normal leukocytes, their expression pattern seems to be wider than to be attributed to the CT gene family. Future research should focus on the expression profiles of so called CT antigens to find those with more testis specific expression.

Expression of Cancer-Testis Antigens in Stem Cells: Is it a Potential Drawback or an Advantage in Cancer Immunotherapy

  • Ghafouri-Fard, Soudeh
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.7
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    • pp.3079-3081
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    • 2015
  • Cancer-testis antigens (CTAs) are a group of tumor associated antigens with a restricted expression pattern in normal gametogenic tissues but expression in a broad range of malignancies. Their expression pattern has made them potential targets for immunotherapy. However, expression of some of these antigens has been demonstrated in normal stem cells as well as cancer stem cells (CSCs). As CSCs have been shown to be sources of metastasis and tumor recurrence, novel therapies are being focused on their eradication. On the other hand, CTA expression in normal stem cells raises the possibility that CTA based immunotherapies cause side effects in normal tissues.

Expression of Cancer-Testis Antigens in Pediatric Cancers

  • Ghafouri-Fard, Soudeh
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.13
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    • pp.5149-5152
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    • 2015
  • Cancer-testis antigens (CTAs) are a group of tumor-associated antigens with more than 140 members whose expression has been shown to be limited to gametogenic tissues and placenta among normal tissues. However, malignant tissues of different origins have shown aberrant and elevated expression of these antigens. Such a pattern of expression endows beneficial properties for use as cancer biomarkers as well as immunotherapeutic targets as a result of the immune-privileged status of the testes. CTAs have been shown to be expressed in pediatric brain tumors, different types of sarcomas, leukemias, and lymphomas as well as neuroblastomas. Although data regarding their expression pattern in childhood tumors are not as comprehensive as for adult tumors, it is supposed that CTA-based immunotherapeutic approaches can also be used for pediatric cancers. However, there are limited data about the objective clinical responses following immunotherapy in such patients. Here we try to review the available information.