Cloning of a novel EGFR-related peptide: a putative negative regulator of EGFR

• Published in: American Journal of Physiology: Cell Physiology 2001-05, Vol.280 (5), p.C1083-C1089
• Main Authors: Yu, Yingjie, Rishi, Arun K, Turner, Jerrold R, Liu, Dayou, Black, Eric D, Moshier, Jeffrey A, Majumdar, Adhip P. N
• Format: Article
• Language: English
• Subjects: 5' Untranslated Regions - genetics; Amino Acid Sequence; Animals; Cell Division; Cloning, Molecular; Duodenum; Gastric Mucosa - physiology; Gene Expression Regulation - physiology; Glycoproteins - chemistry; Glycoproteins - genetics; Glycoproteins - physiology; Humans; Intestinal Mucosa - physiology; Molecular Sequence Data; Organ Specificity; Rats; Receptor, Epidermal Growth Factor - chemistry; Receptor, Epidermal Growth Factor - genetics; Receptor, ErbB-2; Recombinant Proteins - metabolism; RNA, Messenger - genetics; Sequence Alignment; Sequence Homology, Amino Acid; Transcription, Genetic; Transfection; Tumor Cells, Cultured
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.2001.280.5.C1083

2  Veterans Affairs Medical Center, 3  Karmanos Cancer Institute, and Departments of 1  Internal Medicine, 4  Pathology, and 6  Biochemistry and Molecular Biology, 5  Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan 48201 Although epidermal growth factor receptor (EGFR) plays a key role in regulating cell proliferation, differentiation, and transformation in many tissues, little is known about the factor(s) that may modulate its function. We have isolated a cDNA clone from the rat gastroduodenal mucosa whose full length revealed 1,958 bp that contained 227 bp of 5'-untranslated region (UTR) and an open-reading frame encoding 479 amino acids, followed by 290 bp of 3'-UTR. It showed ~85% nucleotide homology to the external domain of the rat EGFR. We refer to the product of the newly isolated cDNA as EGFR-related protein (ERRP). In Northern blot analysis with poly(A) + RNA from different rat tissues, ERRP cDNA hybridized to several mRNA transcripts with the strongest reaction noted with a transcript of ~2 kb. Maximal expression of the 2-kb mRNA transcript was observed in the small intestine, followed by colon, liver, gastric mucosa, and other tissues. Transfection of ERRP cDNA into a colon cancer cell line, HCT116, resulted in a marked reduction in proliferation in monolayer and colony formation in soft agar compared with the vector-transfected controls. In another colon cancer cell line, Caco-2, with a tetracycline-regulated promoter system, induction of ERRP expression in the absence of doxycycline was associated with a marked reduction in EGFR activation and proliferation. We conclude that the ERRP cDNA may represent a new member of the EGFR gene family and that ERRP plays a role in regulating cell proliferation by modulating the function of EGFR. cell proliferation; epidermal growth factor receptor; complementary deoxyribonucleic acid; epidermal growth factor receptor-related protein