RhCG is downregulated in oesophageal squamous cell carcinomas, but expressed in multiple squamous epithelia.
To better understand the molecular events underlying the development of oesophageal cancer, we have isolated the genes dysregulated in primary oesophageal cancer tissues using a modified differential display polymerase chain reaction (DD-PCR). In the present study, a gene designated C15orf6 was identified. The C15orf6 gene, encompassing 25 kb, is composed of 11 exons with a mRNA of 1948 bp. Database searching showed that C15orf6 was 100% homologous to the Rh type C-glycoprotein (RhCG) with the same open reading frame, but 16 bp longer than RhCG at the 5'-end. The gene was highly expressed in human oesophagus, cervix, oral cavity, skin and kidney, but undetectable in the other 14 adult normal tissues examined. Northern blot, RT-PCR and western blot analysis showed that RhCG/C15orf6 was frequently lost or dramatically reduced in primary oesophageal cancer tissues (30/34) compared with the corresponding normal oesophageal mucosa. Three oesophageal-cancer cell lines tested lacked RhCG/C15orf6 expression. Immunohistochemistry revealed that in normal oesophageal tissues, RhCG/C15orf6 was mainly expressed in the plasma membrane of the epithelial cells. In addition, Rh-associated glycoprotein (RhAG) expression was also commonly silenced in both oesophageal cancer cell lines (2/3) and primary oesophageal cancer tissues (11/13). To our knowledge, this is the first time that RhAG expression has been seen in oesophageal epithelium and extends the functional role of the RhAG protein beyond the erythrocyte. These data suggest that inactivation of RhCG/C15orf6 and RhAG occurs frequently during the development of human oesophageal cancer.
Chen
Bao-Sheng
BS
National Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Xu
Zhi-Xiong
ZX
Xu
Xin
X
Cai
Yan
Y
Han
Ya-Ling
YL
Wang
Jie
J
Xia
Shu-Hua
SH
Hu
Hai
H
Wei
Fang
F
Wu
Min
M
Wang
Ming-Rong
MR
D000595:Amino Acid Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D027682:Cation Transport Proteins; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000379:methods; D012334:RNA, Neoplasm / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D027682:Cation Transport Proteins; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C413213:RHCG protein, human; D012334:RNA, Neoplasm