title: TSLC1 is a tumor suppressor gene associated with metastasis in nasopharyngeal carcinoma.
abstract: 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 G(0)-G(1) 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.
authors.affiliation: Department of Biology and Center for Cancer Research, Hong Kong University of Science and Technology, Kowloon, Hong Kong (SAR), People's Republic of China.
authors.forename: Hong Lok
authors.initials: HL
authors.lastname: Lung
authors.forename: Arthur Kwok Leung
authors.initials: AK
authors.lastname: Cheung
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
authors.forename: Yue
authors.initials: Y
authors.lastname: Cheng
authors.forename: Fung Mei
authors.initials: FM
authors.lastname: Kwong
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Murakami
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Guan
authors.forename: Jonathan Shuntong
authors.initials: JS
authors.lastname: Sham
authors.forename: Daniel
authors.initials: D
authors.lastname: Chua
authors.forename: Alexey I
authors.initials: AI
authors.lastname: Protopopov
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Zabarovsky
authors.forename: Sai Wah
authors.initials: SW
authors.lastname: Tsao
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Stanbridge
authors.forename: Maria Li
authors.initials: ML
authors.lastname: Lung
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology / Q000556:secondary*; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D045744:Cell Line, Tumor / Q000166:cytology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D007136:Immunoglobulins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008207:Lymphatic Metastasis / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D009363:Neoplasm Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009368:Neoplasm Transplantation; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection; D014410:Tumor Stem Cell Assay; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: C403514:CADM1 protein, human; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D016895:Culture Media, Serum-Free; D007136:Immunoglobulins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D025521:Tumor Suppressor Proteins