Cloning of a novel EGFR-related peptide: a putative negative regulator of EGFR.
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 approximately 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.
Yu
Y
Y
Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Rishi
A K
AK
Turner
J R
JR
Liu
D
D
Black
E D
ED
Moshier
J A
JA
Majumdar
A P
AP
D020121:5' Untranslated Regions / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division; D003001:Cloning, Molecular; D004386:Duodenum; D066246:ErbB Receptors / Q000737:chemistry / Q000235:genetics*; D005753:Gastric Mucosa / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007413:Intestinal Mucosa / Q000502:physiology*; D008969:Molecular Sequence Data; D009928:Organ Specificity; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D020121:5' Untranslated Regions; D066246:ErbB Receptors; D006023:Glycoproteins; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011994:Recombinant Proteins; C512478:EGFR protein, human; C483803:Egfr protein, rat; C483804:Erbb2 protein, rat