TY - JOUR
T1 - TSLC1 is a tumor suppressor gene associated with metastasis in nasopharyngeal carcinoma
AU - Lung, Hong Lok
AU - Cheung, Arthur Kwok Leung
AU - Xie, Dan
AU - Cheng, Yue
AU - Kwong, Fung Mei
AU - Murakami, Yoshinori
AU - Guan, Xin Yuan
AU - Sham, Jonathan Shuntong
AU - Chua, Daniel
AU - Protopopov, Alexey I.
AU - Zabarovsky, Eugene R.
AU - Tsao, Sai Wah
AU - Stanbridge, Eric J.
AU - Lung, Maria Li
N1 - Funding information:
The Research Grants Council of the Hong Kong Special Administrative Region, People's Republic of China: Grant number HKUST 6113/01M and CA03/04.01 to M.L. Lung and the Swedish Cancer Society, the Swedish Research Council, STINT, the Swedish Institute, the Royal Swedish Academy of Sciences and INTAS to E.R. Zabarovsky.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
We thank Prof. Yan Fang (State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-Sen University, Guangzhou, People's Republic of China) for providing us the NPC specimens for tissue microarray analysis.
Publisher copyright:
©2006 American Association for Cancer Research
PY - 2006/10/1
Y1 - 2006/10/1
N2 - In up to 87% of nasopharyngeal carcinoma (NPC) clinical tumor specimens, there was either down-regulation or loss of TSLC1 gene expression. Using a tissue microarray and immunohistochemical staining, the frequency of down-regulated or loss of expression of TSLC1 in metastatic lymph node NPC was 83% and the frequency of loss of expression of TSLC1 was 35%, which was significantly higher than that in primary NPC (12%). To examine the possible growth-suppressive activity of TSLC1 in NPC, three NPC cell lines, HONE1, HNE1, and CNE2, were transfected with the wild-type TSLC1 gene cloned into the pCR3.1 expression vector; a reduction of colony formation ability was observed for all three cell lines. A tetracycline-inducible expression vector, pETE-Bsd, was also used to obtain stable transfectants of TSLC1. There was a dramatic difference between colony formation ability in the presence or absence of doxycycline when the gene is shut off or expressed, respectively, with the tetracycline-inducible system. Tumorigenicity assay results show that the activation of TSLC1 suppresses tumor formation in nude mice and functional inactivation of this gene is observed in all the tumors derived from tumorigenic transfectants. Further studies indicate that expression of TSLC1 inhibits HONE1 cell growth in vitro by arresting cells in G0-G1 phase in normal culture conditions, whereas in the absence of serum, TSLC1 induced apoptosis. These findings suggest that TSLC1 is a tumor suppressor gene in NPC, which is significantly associated with lymph node metastases.
AB - In up to 87% of nasopharyngeal carcinoma (NPC) clinical tumor specimens, there was either down-regulation or loss of TSLC1 gene expression. Using a tissue microarray and immunohistochemical staining, the frequency of down-regulated or loss of expression of TSLC1 in metastatic lymph node NPC was 83% and the frequency of loss of expression of TSLC1 was 35%, which was significantly higher than that in primary NPC (12%). To examine the possible growth-suppressive activity of TSLC1 in NPC, three NPC cell lines, HONE1, HNE1, and CNE2, were transfected with the wild-type TSLC1 gene cloned into the pCR3.1 expression vector; a reduction of colony formation ability was observed for all three cell lines. A tetracycline-inducible expression vector, pETE-Bsd, was also used to obtain stable transfectants of TSLC1. There was a dramatic difference between colony formation ability in the presence or absence of doxycycline when the gene is shut off or expressed, respectively, with the tetracycline-inducible system. Tumorigenicity assay results show that the activation of TSLC1 suppresses tumor formation in nude mice and functional inactivation of this gene is observed in all the tumors derived from tumorigenic transfectants. Further studies indicate that expression of TSLC1 inhibits HONE1 cell growth in vitro by arresting cells in G0-G1 phase in normal culture conditions, whereas in the absence of serum, TSLC1 induced apoptosis. These findings suggest that TSLC1 is a tumor suppressor gene in NPC, which is significantly associated with lymph node metastases.
UR - http://www.scopus.com/inward/record.url?scp=33750331446&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-06-0590
DO - 10.1158/0008-5472.CAN-06-0590
M3 - Journal article
C2 - 17018592
AN - SCOPUS:33750331446
SN - 0008-5472
VL - 66
SP - 9385
EP - 9392
JO - Cancer Research
JF - Cancer Research
IS - 19
ER -