Oncogenic properties of a novel gene JK-1 located in chromosome 5p and its overexpression in human esophageal squamous cell carcinoma.
Esophageal squamous cell carcinoma (ESCC) shows high frequency and mortality in Asian regions, including China. Previous analysis of genomic DNA of ESCC using comparative genomic hybridization indicated that amplification of the chromosome 5p regions is a common event in ESCC cell lines and patient cases of Hong Kong Chinese origin, and the results suggested that the genes located in the chromosome 5p regions may play crucial roles in the molecular pathogenesis of ESCC. Our previous studies on ESCC confirmed the tumorigenic and overexpression properties of a novel gene JS-1 located in chromosome 5p15.2 upstream to delta-catenin. In the present study, another novel gene JK-1 which is located at 5p15.1 downstream to delta-catenin was characterized for its roles in the pathogenesis of ESCC. Thirteen ESCC cell lines and 30 surgical specimens of esophageal tumors were studied for the overexpression of JK-1 using multiplex RT-PCR analysis. The transforming capacity of overexpression of JK-1 was also investigated by transfecting NIH 3T3 and HEK 293 cells with the expression vector cloned with JK-1, followed by the soft agar and foci formation assays. JK-1 was overexpressed in 9/13 (69%) of the ESCC cell lines and 9/30 (30%) of the ESCC patient cases. Both NIH 3T3 and HEK 293 cells acquired the properties of anchorage-dependent and -independent growth when JK-1 was overexpressed. Most significantly, subcutaneous sarcomas were formed in all (3/3) the athymic nude mice after NIH 3T3 cells overexpressing JK-1 were injected subcutaneously. Our results thus indicated that JK-1 is commonly overexpressed in ESCC and has a prominent capacity to transform normal cells. Our overall results thus provide the first evidence that the overexpression of JK-1 and its transforming capacity in normal cells may play a critical role in the molecular pathogenesis of ESCC.
Tang
Wing K
WK
Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, P.R. China.
Chui
Chung H
CH
Fatima
Sarwat
S
Kok
Stanton H L
SH
Pak
Kai C
KC
Ou
Tian M
TM
Hui
Kin S
KS
Wong
Mei M
MM
Wong
John
J
Law
Simon
S
Tsao
S W
SW
Lam
King Y
KY
Beh
Philip S L
PS
Srivastava
Gopesh
G
Chan
Albert S C
AS
Ho
Kwok P
KP
Tang
Johnny C O
JC
D000368:Aged; D000818:Animals; D015197:Carcinogenicity Tests; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5; D004938:Esophageal Neoplasms / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D041681:NIH 3T3 Cells; D009363:Neoplasm Proteins / Q000235:genetics*; D009857:Oncogenes / Q000502:physiology; D014407:Tumor Cells, Cultured
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C522691:RETREG1 protein, human