Molecular and genetic characterization of a non-metastatic human esophageal cancer cell line, T.Tn expressing non-functional mutated p53.
Lymph node metastasis is commonly found in esophageal squamous cell carcinoma (SCC). In this study, we examined the molecular and genetic characteristics of a human esophageal SCC cell line, T.Tn. T.Tn cells formed tumors at s.c. tissue in nude mice when inoculated with Matrigel, but did not metastasize to any organs. T.Tn cells expressed low level of proMMP2 and a trace level of proMMP9. However, T.Tn cells expressed high level of TIMP1 and TIMP2, and beta-catenin and E-cadherin. We found a point mutation of p53 gene at codon 213 (CAT-->CGT) in T.Tn cells. The mutated-p53 protein did not show transcriptional activity on p21(waf1), MDM2 and Bax promoters. Thus, T.Tn cells are low tumorigenic and weakly invasive but not metastasizing in nude mice, and T.Tn cells are suitable parental cells for establishing a model system to study invasion and metastasis of esophageal SCC.
Sakai
Taro
T
Department of Surgical and Molecular Pathology, Dokkyo University School of Medicine, 880 Kitakobayashi, Mibu, Shimotsuga, Tochigi 321-0293, Japan.
Furihata
Tadashi
T
Kawamata
Hitoshi
H
Omotehara
Fumie
F
Shinagawa
Yasuhiro
Y
Imura
Johji
J
Kubota
Keiichi
K
Terano
Akira
A
Fujimori
Takahiro
T
D000818:Animals; D015820:Cadherins / Q000096:biosynthesis; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology* / Q000556:secondary; D002455:Cell Division / Q000502:physiology; D017364:Collagenases / Q000096:biosynthesis; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics; D004792:Enzyme Precursors / Q000096:biosynthesis; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D018093:Gelatinases / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000096:biosynthesis; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis / Q000378:metabolism; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics; D015533:Transcriptional Activation; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D051176:beta Catenin
C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D015820:Cadherins; D003598:Cytoskeletal Proteins; D004792:Enzyme Precursors; D019715:Tissue Inhibitor of Metalloproteinase-1; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; D019716:Tissue Inhibitor of Metalloproteinase-2; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; C120487:pro-matrix metalloproteinase 9; C069860:progelatinase; D020780:Matrix Metalloproteinase 9