THY1 is a candidate tumour suppressor gene with decreased expression in metastatic nasopharyngeal carcinoma

Abstract

Using oligonucleotide microarray analysis, THY1, mapping close to a previously defined 11q22-23 nasopharyngeal carcinoma (NPC) critical region was identified as showing consistent downregulated expression in the tumour segregants, as compared to their parental tumour-suppressing microcell hybrids (MCHs). Gene expression and protein analyses show that THY1 was not expressed in the NPC HONE1 recipient cells, tumour segregants, and other NPC cell lines; THY1 was exclusively expressed in the non-tumourigenic MCHs. The mechanism of THY1 gene inactivation in these cell lines was attributed to hypermethylation. Clinical study showed that in 65% of NPC specimens there was either downregulation or loss of THY1 gene expression. Using a tissue microarray and immunohistochemical staining, 44% of the NPC cases showed downregulated expression of THY1 and 9% lost THY1 expression. The frequency of THY1 downregulated expression in lymph node metastatic NPC was 63%, which was significantly higher than in the primary tumour (33%). After transfection of THY1 gene into HONE1 cells, a dramatic reduction of colony formation ability was observed. These findings suggest that THY1 is a good candidate tumour suppressor gene in NPC, which is significantly associated with lymph node metastases.

Differential expression of CD90 and CD14 stem cell markers in malignant breast cancer cell lines

“…This protein is involved in T-cell activation (23) and has widespread nonimmunologic functions, including inhibition of neurite outgrowth (24), apoptotic signaling (25), leukocyte and melanoma cell adhesion and migration (26,27), tumor suppression (28,29), and fibroblast proliferation and migration (30)(31)(32). It is an important marker of mesenchymal stem cells being associated with development, cancer, and CSC.…”

Catalytic activity of matrix metalloproteinase‐19 is essential for tumor suppressor and anti‐angiogenic activities in nasopharyngeal carcinoma

“…Western blotting was performed as previously described. 18 In brief, samples were separated by SDS-PAGE and transferred to PVDF membrane (Millipore). Primary antibodies against the MMP19 N-terminus (1:1000; M5559, Sigma) and VEGF (1:500; SC-152, Santa Cruz Biotechnology) were used.…”

“…12 pCR3.1/MMP19 WT, pCR3.1/MMP19 EA, and pCR3.1 were transiently transfected into NPC cell lines with Lipofectamine 2000 reagent (Invitrogen) to perform the CFA as previously described. 18 In brief, selective medium with 500 lg/ml G418 was added until the negative control (cells without plasmid transfection) died completely. The cells were then fixed with 4% formaldehyde for 4 hr and stained with 1:50 Giemsa stain solution overnight.…”

“…For the establishment of stable MMP19 clones, pETE/MMP19 WT and EA plasmids were similarly transfected into HONE1-2 using Lipofectamine 2000 reagent (Invitrogen), selected and maintained in 500 lg/ml G418 and 5 lg/ml blasticidin as previously described. 18 Nude mouse tumorigenicity assay…”

Lactotransferrin: A candidate tumor suppressor—Deficient expression in human nasopharyngeal carcinoma and inhibition of NPC cell proliferation by modulating the mitogen‐activated protein kinase pathway

“…[5][6][7] In addition, the BLU/ZMYND10 and THY1 genes may act as tumor suppressors associated with the regulation of tumorigenesis and lymph node metastasis of NPC. 8,9 Therefore, isolation and identification of new susceptibility genes for NPC from chromosome 3p21 may provide insights into understanding the molecular and genetic basis of NPC.…”