A tumorigenic homeobox (HOX) gene expressing human gastric cell line derived from putative gastric stem cell.
OBJECTIVE
Study the mechanism of gastric tumor development.


BACKGROUND
We have generated and characterized a novel human gastric cell line, KMU-CS12 (CS12), from an immortal cell line, KMU-CSN (CSN; formerly named as GI2CS) which was derived from putative human gastric stem cell/progenitor cell clone, KMU-GI2.


METHODS
The characterization of the CS12 cell line includes gene expression by immunocytochemical staining, cell proliferation and differentiation potential, cyotogenetic analysis by Giemsa banding and spectral karyotype analysis (SKY), and tumorigenicity in immune-deficient congenic inbred, nude mice (BALB/cAnN-Foxn1nu/CrlNarl). The Agilent Human 1A oligo-array and RT-PCR were also employed to analyze the expression of homeobox (HOX) genes.


RESULTS
The CS12 gastric cell line showed cancer cell phenotypes, i.e. the ability of anchorage-independent growth high frequency (44%) and to the expression of Oct-4, a transcription factor expressed in embryonic stem cells and many types of cancer cells, and tumor development in immune deficient mice. SKY analysis indicated a characteristic duplication of the short arm of chromosome 7 to chromosome 12. Agilent Human 1A oligo-array analysis showed that the expression of 1145 genes was upregulated while that of 890 genes was downregulated in CS12 cells. RT-PCR revealed that homeobox genes (HOXA4, HOXA5, HOXA7, HOXA9, and HOXA13) were highly expressed in CS12 cells in culture, as well as tumor tissues developed by CS12 cells in immunodeficient mice for six to eight weeks.


CONCLUSIONS
Except for the duplication of the short arm of Chromosome 7 on Chromosome12, the karyotype of the tumorigenic CS12 cells is similar to the parental GI2 cells which are non-tumorigenic and normal in karyotype. This chromosomal change could be the cause for the high expression of HOXA genes and tumorigenicity of these cells found in this study. Thus HOXA genes might play an important role in gastric carcinogenesis.
Yang
Yuan-Chieh
YC
Department of Laboratory Medicine, Graduate Institute of Medicine, I-Shou University, Taipei, Taiwan.
Wang
Sheng-Wen
SW
Wu
I-Chen
IC
Chang
Chia-Cheng
CC
Huang
Yeou-Lih
YL
Lee
Oscar K
OK
Chang
Jan-Gowth
JG
Chen
Angela
A
Kuo
Fu-Chen
FC
Wang
Wen-Ming
WM
Wu
Deng-Chyang
DC
D000818:Animals; D045744:Cell Line, Tumor / Q000473:pathology*; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D005801:Genes, Homeobox / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation