[Show abstract][Hide abstract] ABSTRACT: 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.
European Journal of Cancer 10/2002; 38(14):1927-36. DOI:10.1016/S0959-8049(02)00190-9 · 4.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: cDNA fragments that were differentially expressed between human oesophageal carcinomas and matched normal adjacent mucosa were isolated using an improved mRNA differential display technique. One of them was identified as the 3′-untranslated region of SPRR3 and was homologous to the esophagin cDNA. Northern blot, dot blot and reverse transcription–polymerase chain reaction (RT–PCR) analyses revealed that SPRR3 expression was lost in three cell lines of oesophageal carcinoma and was dramatically decreased in 54 out of 57 primary oesophageal carcinomas compared with adjacent normal mucosa. Esophagin has been shown to be down-regulated in western oesophageal carcinomas. The data suggest that esophagin is probably the protein product of the gene SPRR3 and that altered mRNA expression of SPRR3 / esophagin is a frequent event in the development of Chinese oesophageal cancer.