title: Polyoma middle T antigen or v-src desensitizes human epidermal growth factor receptor function and interference by a monensin-resistant mutation in mouse Balb/3T3 cells.
abstract: Epidermal growth factor (EGF)-induced down-regulation of its receptor is an obligatory pathway for cellular regulation of EGF-specific receptor (EGF-R) in normal and malignant cells. BNER4 cells are mouse Balb/3T3 cells transfected with the human EGF-R complementary DNA (cDNA). Polyoma middle T antigen-transfectants of BNER4, B4/MT-2, B4/MT-13, B4/MT-23, and B4/MT-24, showed diminished down-regulation of cell surface human EGF-R in response to EGF relative to the parental BNER4 cells. Also, the v-src-transfectants B4/SRC-13 and B4/SRC-24 showed much less down-regulation than BNER4 cells, whereas H-ras-transfectants of BNER4, B4/RAS-24 and B4/RAS-25, showed EGF-induced down-regulation of the cell surface EGF-R similar to that of BNER4. EGF induced DNA synthesis more than 20-fold in BNER4, but induced only about a 1.5- to 6-fold increase in the middle T antigen- and v-src-transfectants. EGF-Rs of the middle T antigen-transfectants were metabolically stable in the presence of EGF in comparison with their parental BNER4 cells. EGF-Rs of BNER4 cells degraded with half-lives of about 2 h in the presence of EGF, but those of the middle T antigen transformants were found to be highly stabilized in the presence of EGF. On the other hand, transfection with polyoma middle T antigen (MTAg) cDNA causes malignant transformation of Balb/3T3 cells, but not its monensin (an ionophoric antibiotic)-resistant mutant MO-5 cells, which have no significant EGF binding activity. Transfection of human EGF-R cDNA into MO-5 leads to the expression of high levels of human EGF-R in MNER31. Unlike the polyoma MTAg transfectants of BNER4, EGF-R in polyoma MTAg cDNA-transfectants into MNER31, M31/MT-13 and M31/MT-14, were down-regulated to levels similar to those of their parental MNER31. Exposure to EGF induced a more than 10-fold increase in DNA synthesis of quiescent BNER4, MNER31, M31/MT-13, and M31/MT-14 cells. Polyoma middle T antigen or v-src appears to modulate EGF-induced down-regulation of EGF-R, possibly through interaction of the receptor with the viral oncogenes, and this interaction may be altered in the mutant.
authors.affiliation: Department of Biochemistry, Oita Medical University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ono
authors.forename: Y
authors.initials: Y
authors.lastname: Nakayama
authors.forename: G
authors.initials: G
authors.lastname: Princler
authors.forename: J
authors.initials: J
authors.lastname: Gopas
authors.forename: H F
authors.initials: HF
authors.lastname: Kung
authors.forename: M
authors.initials: M
authors.lastname: Kuwano
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000502:physiology*; D001483:Base Sequence; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D004247:DNA / Q000096:biosynthesis; D015536:Down-Regulation; D004351:Drug Resistance; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D066246:ErbB Receptors / Q000235:genetics / Q000502:physiology*; D016391:Genes, src; D051379:Mice; D008969:Molecular Sequence Data; D008985:Monensin / Q000494:pharmacology; D009154:Mutation; D010766:Phosphorylation; D014162:Transfection
chemical_list: D000952:Antigens, Polyomavirus Transforming; D004815:Epidermal Growth Factor; D004247:DNA; D008985:Monensin; D066246:ErbB Receptors