Yau Wing Lung, Lung Hong Lok, Zabarovsky Eugene R, Lerman Michael I, Sham Jonathan Shun-Tong, Chua Daniel Tsin-Tien, Tsao Sai Wah, Stanbridge Eric J, Lung Maria Li
Department of Biology and Center for Cancer Research, The Hong Kong University of Science and Technology, Hong Kong (SAR), China.
Int J Cancer. 2006 Dec 15;119(12):2821-6. doi: 10.1002/ijc.22232.
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.
3号染色体短臂在包括鼻咽癌（NPC）在内的多种癌症的肿瘤发生过程中发挥着重要作用。我们之前通过单染色体转移方法表明3号染色体短臂能够在体内抑制肿瘤生长，这表明3p21.3区域对肿瘤抑制至关重要。BLU/ZMYND10是位于3p21.3关键区域的候选肿瘤抑制基因之一，也是鼻咽癌的候选抑癌基因。通过定量逆转录聚合酶链反应（RT-PCR）检测发现，它在NPC细胞系（83%）和NPC活检组织（80%）中经常下调。然而，尚无功能研究证实BLU/ZMYND10作为肿瘤抑制基因的功能作用。在本研究中，利用四环素调控系统进行基因失活试验（GIT）来研究BLU/ZMYND10的功能作用。当在无强力霉素的情况下表达BLU/ZMYND10时，稳定转染子能够在裸鼠中诱导肿瘤抑制。相反，通过强力霉素处理下调这些肿瘤抑制克隆中的BLU/ZMYND10可恢复肿瘤形成能力。本研究提供了首个重要证据，证明BLU/ZMYND10能够在体内功能性地抑制肿瘤形成，因此很可能是参与鼻咽癌的候选肿瘤抑制基因之一。
