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1. Preethi Devanand. Epigenetic regulation of BTG2/TIS21/PC3 and its tumor suppressive role in invasive human cancers.

Degree: 2018, Ajou University

B cell translocation gene 2 (BTG2/TIS21/PC3) belongs to the family of antiproliferative (APRO) genes and reported as a tumor suppressor by our group and others. Expression of BTG2 is significantly reduced in cancers developed in various organs and tissues. EJ (bladder carcinoma cells), MKN-1 (gastric cancer cells) are highly invasive and metastatic cells with very less endogenous BTG2 expression due to epigenetic regulation. Significantly lower endogenous expression of BTG2 was observed in human muscle-invasive bladder cancers (MIBC) than matched normal tissues and non-muscle invasive bladder cancers (NMIBC). BTG2 expression was inversely correlated with increased expression of the DNA methyltransferases DNMT1 and DNMT3a in MIBC, but not NMIBC, suggesting a potential role for BTG2 expression in muscle invasion of bladder cancer. Over 90% of tumor tissues revealed strong methylation at CpG islands of the BTG2 gene, compared with no methylation in the normal tissues, implying epigenetic regulation of BTG2 expression in bladder carcinogenesis. BTG2 is constitutively expressed in mucous epithelium and parietal cells of gastric glands in stomach, and the expression was increased in mucous epithelium with H. pylori infection as opposed to loss in human gastric adenocarcinoma. Indeed, adenoviral transduction of BTG2 significantly inhibited Tipα activity in MKN-1 and MGT-40, human and mouse gastric cancer cells, respectively, thereby downregulated TNFα expression and Erk1/2 phosphorylation via reducing nucleolin, Tipα receptor, expression. Chromatin immunoprecipitation proved that BTG2 inhibited Sp1 expression and it’s binding to the promoter of nucleolin gene. In addition, BTG2 expression significantly reduced membrane localized nucleolin expression in cancer cells and the loss of BTG2/TIS21 expression rather induced cytoplasmic nucleolin availability in gastric cancer tissues, evidenced by immunoblot and immunohistochemistry. The higher expression of BTG2 and the lower nucleolin expression accompanied with the better overall survival of the poorly differentiated gastric cancer patients.

B cell translocation gene 2(BTG2/TIS21/PC3)는 antiproliferative gene(APRO) 계열에 속하며 본 연구팀을 포함한 많은 연구자들에 의해 BTG2 의 암억제 기능이 연구되어 왔다. BTG2 는 여러 조직과 기관에서 발생한 암에서 그 발현이 감소되어 있고, 특히 침윤(invasion)과 전이(metastasis)를 잘하는 암세포인 EJ (bladder carcinoma cells)와 MKN-1 (gastric cancer cells)에서도 후성유전학적(epigenetic regulation)으로 BTG2 발현이 매우 감소되어 있다. 최근 사람에서, 이런 침윤성과 전이성이 높은 암에서 BTG2 가 침윤을 억제하고 침윤을 조장하는 단백질과 mRNA 발현과는 음의 상관도를 보인다는 보고가 많기에, 본 저자는 BTG2 가 어떤 기전으로 침윤성 암을 조절하는지를 중점적으로 연구하였다. 사람의 근육침범 방광암(muscleinvasive bladder cancers, MIBC)에서 비-근육침범 방광암(non-muscle invasive bladder cancers, NMIBC)보다 BTG2 의 발현이 현저히 감소되어 있다는 것을 발견하였다. 이런 MIBC 에서의 BTG2 의 감소는 반대로 DNA 메틸기전달효소 DNMT1 과 DNMT3a 의 증가와 연관이 있었고, 이런 음의 상관관계는 NMIBC 에서는 발견되지 않음으로써 BTG2 이 방광암의 근육 침범에 분명한 역할을 하고 있다는 가능성을 보였다. 방광암 조직들의 90%에서 BTG2 유전자의 CpG 섬에 강한 메틸화를 보였고, 반대로 정상 방광조직에서는 메틸화가 발견되지 않음으로써, 방광암발생과정에서 BTG2 이 후성학적 조절을 받는다는 사실도 증명했다. 한편, BTG2 는 위 점막의 상피세포와 위샘의 벽세포(Parietal cell)에서 기본적으로 발현되고 있으며, 이 유전자의 발현은…

Advisors/Committee Members: 대학원 의생명과학과, 201024529, Preethi Devanand.

Subjects/Keywords: BTG2; 침윤성 암; DNMT; H. pylori; TNFα

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APA (6th Edition):

Devanand, P. (2018). Epigenetic regulation of BTG2/TIS21/PC3 and its tumor suppressive role in invasive human cancers. (Thesis). Ajou University. Retrieved from http://repository.ajou.ac.kr/handle/201003/16536 ; http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000027461

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Devanand, Preethi. “Epigenetic regulation of BTG2/TIS21/PC3 and its tumor suppressive role in invasive human cancers.” 2018. Thesis, Ajou University. Accessed January 23, 2019. http://repository.ajou.ac.kr/handle/201003/16536 ; http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000027461.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Devanand, Preethi. “Epigenetic regulation of BTG2/TIS21/PC3 and its tumor suppressive role in invasive human cancers.” 2018. Web. 23 Jan 2019.

Vancouver:

Devanand P. Epigenetic regulation of BTG2/TIS21/PC3 and its tumor suppressive role in invasive human cancers. [Internet] [Thesis]. Ajou University; 2018. [cited 2019 Jan 23]. Available from: http://repository.ajou.ac.kr/handle/201003/16536 ; http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000027461.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Devanand P. Epigenetic regulation of BTG2/TIS21/PC3 and its tumor suppressive role in invasive human cancers. [Thesis]. Ajou University; 2018. Available from: http://repository.ajou.ac.kr/handle/201003/16536 ; http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000027461

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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