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EBV Conference 2008 Guangzhou - Baylor College of Medicine

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37 (RegID: 1062)<br />

Maria Lung<br />

Institution: Hong Kong University <strong>of</strong> Science & Technology<br />

e-mail: bomaria@ust.hk<br />

FUNCTIONAL CHARACTERIZATION OF A CHROMOSOME 11 CANDIDATE TUMOR<br />

SUPPRESSOR GENE, THY1, IN NASOPHARYNGEAL CARCINOMA<br />

HL Lung, AKL Cheung, Y Cheng, FM Kwong, PHY Lo, EWL Law, D Chua, ER Zabarovsky, N Wang,<br />

SW Tsao, EJ Stanbridge, ML Lung<br />

Oralabstract:<br />

Previous studies on identifying chromosome 11 critical regions associated with functional suppression <strong>of</strong><br />

tumor formation in nasopharyngeal carcinoma (NPC) utilized a monochromosome transfer and<br />

complementation approach, which successfully identified several candidate tumor suppressor genes (TSGs)<br />

mapping to chromosome 11q22-q23. These include CADM1 (Cell Adhesion Molecule 1, formerly known<br />

as TSLC1), THY1 (THY1 cell surface antigen), and CRYAB (crystalline alpha B). Our previous studies<br />

suggested that THY1 is a good candidate TSG associated with lymph node metastases in NPC. To<br />

examine the tumor-suppressive activity <strong>of</strong> THY1, we have now used the in vivo tumorigenicity assay,<br />

performed using a tetracycline-regulated expression vector system. Tumorigenicity results show that the<br />

activation <strong>of</strong> THY1 suppresses tumor formation <strong>of</strong> HONE1 cells in nude mice. Tumor formation ability<br />

was restored in the presence <strong>of</strong> doxycycline, when the gene is selectively shut <strong>of</strong>f. Additional functional<br />

studies were performed and results indicate expression <strong>of</strong> THY1 inhibits HONE1 cell growth in vitro,<br />

induces cell cycle arrest, reduces anchorage-independent growth, and inhibits cell invasiveness. An<br />

interesting novel link between THY1 and our other two chromosome 11q23 candidate tumor suppressors,<br />

CADM1 and CRYAB, indicate there may be potential collaborative interactions <strong>of</strong> these closely mapping<br />

genes. Gene expression levels <strong>of</strong> CADM1 and CRYAB appear to be tightly regulated by THY1 in HONE1<br />

cells. This possibility is currently being tested.<br />

<strong>EBV</strong> <strong>Conference</strong> <strong>2008</strong> <strong>Guangzhou</strong><br />

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