Esophageal squamous cell carcinoma (ESCC) has a high mortality rate and geographic differences in incidence. Previous studies of comparative genomic hybridization (CGH) showed that chromosomal 5p is frequently amplified in cell lines and primary ESCC of Hong Kong Chinese origin. In this report, attempt was made to study two novel genes, named as
JS-1 and JS-2, which are located in chromosome 5p15.2 and are 5' upstream to
delta catenin for their roles in molecular pathogenesis of ESCC. Eleven cell lines, 27 primary ESCC cases and multiple human tissue
cDNA panels (MTC) of digestive system were studied for the expression level of
JS-1 and JS-2 by RT-PCR. The full-length
cDNA sequences of
JS-1 and JS-2 were determined from a non-
tumor esophageal epithelial cell line by 3' and 5' rapid amplification of
cDNA ends (RACE). The transforming capacity of
JS-1 and JS-2 was also investigated by transfecting NIH 3T3 cells with the expression vector pcDNA3.1(-) cloned with the full coding sequences and it was followed by the study of foci formation of the transfected cells under confluence growth and the anchorage-independent growth in soft
agar. Forty-five percent (5/11) and 18% (2/11) of the ESCC cell lines showed overexpression of
JS-1 and JS-2 respectively, while 55% (15/27) and 14% (3/22) primary ESCC cases showed overexpression of
JS-1 and JS-2 respectively.
JS-1 overexpression was most common in patients with stage II ESCC (6/27; 22%) whereas JS-2 was only overexpressed in a dysplastic lesion (1/22; 4%) and stage III
tumors (2/22; 9%). The expression levels of
JS-1 and JS-2 are both low in normal esophageal tissues. Overexpression of
JS-1 in NIH 3T3 cells caused foci formation in confluence growth and colony formation in soft
agar but not for JS-2. A high grade
sarcoma was formed in the athymic nude mice when NIH 3T3 cells overexpressing
JS-1 were injected subcutaneously. Our results thus indicate that the frequent overexpression of
JS-1 in ESCC and its transforming capacity in normal cells may play a critical role in the molecular pathogenesis of ESCC. The present study also forms the ground work for further identification of novel mechanisms of molecular
carcinogenesis in ESCC and other
cancers.