Role of TGF-beta in EGF-induced transformation of NRK cells is sustaining high-level EGF-signaling.
We have been isolating and analyzing NRK cell mutants, which fail to transform by epidermal growth factor (EGF) and transforming growth factor (TGF)-beta. One such mutant, R14, can respond to the growth inhibitory signal of TGF-beta to the same extent as parental NRK but fail to respond to the growth stimulatory signal of EGF. This mutant has a defect in EGF receptor (EGFR) expression. When R14 mutant expressed a high level of EGFR, however, EGF not only induced proliferation in this mutant but also induced transformation without the aid of TGF-beta. These findings suggest that the major role of TGF-beta in this transformation system should be to counteract the ligand-dependent down-regulation of EGFR, thereby sustaining high-level EGF-signaling.
Kizaka-Kondoh
S
S
Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, Japan. skondoh@virus1.virus.kyoto-u.ac.jp
Akiyama
N
N
Okayama
H
H
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004815:Epidermal Growth Factor / Q000494:pharmacology / Q000502:physiology*; D066246:ErbB Receptors / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D015870:Gene Expression; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D051381:Rats; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology*
D017931:DNA Primers; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D066246:ErbB Receptors