Growth stimulation, altered regulation of epidermal growth factor receptors, and autocrine transformation of spontaneously transformed normal rat kidney cells by transforming growth factor beta.
The tumorigenic NRK-PT14 cell line requires exogenous epidermal growth factor (EGF), but has lost the requirement for transforming growth factor beta (TGF-beta) for anchorage-independent growth, compared to normal rat kidney (NRK) cells. Development of an optimized serum-free medium for the growth of these cells revealed that NRK-PT14 cells also exhibit a qualitatively altered sensitivity to exogenous type 1 TGF-beta, compared to NRK cells. EGF-induced serum-free monolayer growth of NRK-PT14 cells was stimulated 2-fold by TGF-beta under conditions where growth of NRK cells was inhibited by 67%. TGF-beta only stimulated the growth of NRK-PT14 cells when EGF was present and when EGF was added before TGF-beta. In addition, the stimulation of EGF-induced NRK-PT14 cell growth by TGF-beta was associated with a specific, reversible loss of the high-affinity subpopulation of EGF receptors from the surface of these cells. Treatment of NRK cells with TGF-beta resulted in an increase in this EGF receptor population. Finally, EGF-induced anchorage-independent growth of NRK-PT14 cells was shown to be dependent on secreted TGF-beta, demonstrating an autocrine role for TGF-beta in the transformed phenotype of these cells. Autocrine transformation of NRK-PT14 cells by TGF-beta may result directly from the acquisition of an altered (positive) sensitivity to this growth factor.
Nugent
M A
MA
Graduate Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02254.
Lane
E A
EA
Keski-Oja
J
J
Moses
H L
HL
Newman
M J
MJ
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D003470:Culture Media; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D007668:Kidney; D007700:Kinetics; D051381:Rats; D015291:Transforming Growth Factors / Q000494:pharmacology*
D003470:Culture Media; D004815:Epidermal Growth Factor; D015291:Transforming Growth Factors; D066246:ErbB Receptors