Functional studies of the chromosome 3p21.3 candidate tumor suppressor gene BLU/ZMYND10 in nasopharyngeal carcinoma.
Chromosome 3p plays an important role in tumorigenesis in many cancers, including nasopharyngeal carcinoma (NPC). We have previously shown chromosome 3p can suppress tumor growth in vivo by using the monochromosome transfer approach, which indicated the chromosome 3p21.3 region was critical for tumor suppression. BLU/ZMYND10 is one of the candidate tumor suppressor genes mapping in the 3p21.3 critical region and is a candidate TSG for NPC. By quantitative RT-PCR, it is frequently downregulated in NPC cell lines (83%) and NPC biopsies (80%). However, no functional studies have yet verified the functional role of BLU/ZMYND10 as a tumor suppressor gene. In the current study, a gene inactivation test (GIT) utilizing a tetracycline regulation system was used to study the functional role of BLU/ZMYND10. When BLU/ZMYND10 is expressed in the absence of doxycycline, the stable transfectants were able to induce tumor suppression in nude mice. In contrast, downregulation of BLU/ZMYND10 in these tumor suppressive clones by doxycycline treatment restored the tumor formation ability. This study provides the first significant evidence to demonstrate BLU/ZMYND10 can functionally suppress tumor formation in vivo and is, therefore, likely to be one of the candidate tumor suppressor genes involved in NPC.
Yau
Wing Lung
WL
Department of Biology and Center for Cancer Research, The Hong Kong University of Science and Technology, Hong Kong (SAR), China.
Lung
Hong Lok
HL
Zabarovsky
Eugene R
ER
Lerman
Michael I
MI
Sham
Jonathan Shun-Tong
JS
Chua
Daniel Tsin-Tien
DT
Tsao
Sai Wah
SW
Stanbridge
Eric J
EJ
Lung
Maria Li
ML
D000818:Animals; D045744:Cell Line, Tumor; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D003598:Cytoskeletal Proteins; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004318:Doxycycline / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D003598:Cytoskeletal Proteins; D025521:Tumor Suppressor Proteins; C472720:ZMYND10 protein, human; D004318:Doxycycline