Oncogenic properties of a novel gene JK-1 located in chromosome 5p and its overexpression in human esophageal squamous cell carcinoma

Abstract

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 δ-catenin. In the present study, another novel gene JK-1 which is located at 5p15.1 downstream to δ-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.

Physiologic hypoxia promotes maintenance of CML stem cells despite effective BCR-ABL1 inhibition

“…Notably, among these 12 genes, 5 (ARG2, CHI3L1, FAM134B, KRT17, and CD6) have prosurvival functions and/or are associated with transformation and poorer clinical outcome in human cancers. [43][44][45][46][47][48][49] Next, we confirmed that a subset of these genes is dependent on HIF1-a for hypoxia-induced upregulation. As shown in Figure 7B, knockdown of HIF1-a resulted in abrogation of the hypoxia-induced upregulation of ARG2, BNIP3, SULF2, and NEDD9.…”

Stage dependent expression and tumor suppressive function ofFAM134B(JK1) in colon cancer

“…These observations strongly suggest that FAM134B negatively regulates colon cancer growth. In contrast to these results, Tang et al reported that FAM134B promotes cancer cell proliferation and tumor growth in a model derived from oesophageal squamous cell carcinoma . It is worth nothing that other cancer related genes such as cell surface mucin gene family members 11, 12, and 13 (MUC 11, MUC 12, and MUC 13) are also expressed in different ways in colorectal and oesophageal cancers .…”

“…FAM 134B (Family with sequence similarity 134, member B), also called JK1 , is located at chromosome 5p15.1, downstream of δ‐catenin. Our group first reported the importance of this gene in human disease . FAM 134B was noted to play important roles in the pathogenesis of oesophageal squamous cell carcinoma .…”

“…Our group first reported the importance of this gene in human disease . FAM 134B was noted to play important roles in the pathogenesis of oesophageal squamous cell carcinoma . This gene encodes a cis‐golgi transmembrane protein, which is essential for the long‐term survival of nociceptive and autonomic ganglion neurons .…”

Literature and patent analysis of the cloning and identification of human functional genes in China

“…SH3D19 encodes a novel EENbinding protein that can inhibit Ras signaling and that is recruited into the nucleus by the MLL-EEN fusion protein that is believed to play an important role in the onset of leukemia [168]. Furthermore, scientists from the Hong Kong Polytechnic University discovered a candidate oncogene gene FAM134B on the short arm of human chromosome 5 whose overexpression and transforming capacity in normal cells may play a critical role in the molecular pathogenesis of esophageal squamous cell carcinoma (ESCC) [169].…”