Effect of phorbol esters on the activity of purified transforming growth factors

Research output: Contribution to journalArticle

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Abstract

Application of either phorbol esters or transforming growth factors to normal cells in culture may induce the appearance of a malignant phenotype. Since the mechanism of transformation by both chemical tumor promoters and growth factors is unknown, it was of interest to investigate whether phorbol esters might potentiate the activity of transforming growth factors. The combination of β-transforming growth factor (β-TGF) and epidermal growth factor (EGF) causes the normally anchorage-dependent cells (NRK-49F) to form colonies in soft agar. In the presence of maximally stimulating concentrations of EGF and suboptimally stimulating concentrations of β-TGF, phorbol 12-myristate-13-acetate (PMA) enhances the soft agar colony growth of NRK-49F cells in a concentration-dependent manner. However, PMA alone or in combination with either EGF or β-TGF does not stimulate soft agar growth. In contrast to the stimulation of PMA, 4α-phorbol 12,13-didecanoate, an inactive phorbol ester, does not potentiate the effects of EGF plus β-TGF on soft agar growth. PMA does not stimulate the growth of NRK-49F cells in monolayer, nor does it further potentiate the monolayer growth induced by EGF with or without β-TGF. Because the addition to NRK-49F cells of compounds which potentiate β-TGF activity increases EGF receptor number, the effects of PMA on the EGF receptor were studied. A short exposure to PMA (30 min) induces a 50% decrease in EGF receptors of NRK cells whether or not they have been exposed to β-TGF. Scatchard analysis shows that this decrease involves primarily high affinity EGF receptors. However, cells treated with PMA for longer periods of time (4, 6, and 24 h) show no change in EGF or β-TGF receptor binding. PMA therefore must potentiate the activity of purified TGFs without causing an increase in EGF or β-TGF receptor binding.

Original languageEnglish (US)
Pages (from-to)1764-1767
Number of pages4
JournalCancer Research
Volume46
Issue number4
StatePublished - 1986
Externally publishedYes

Fingerprint

Transforming Growth Factors
Phorbol Esters
Epidermal Growth Factor
Acetates
Agar
Growth
Epidermal Growth Factor Receptor
phorbol-12-myristate
Carcinogens
Intercellular Signaling Peptides and Proteins
Cell Culture Techniques
Phenotype

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Effect of phorbol esters on the activity of purified transforming growth factors. / Kraft, Andrew.

In: Cancer Research, Vol. 46, No. 4, 1986, p. 1764-1767.

Research output: Contribution to journalArticle

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abstract = "Application of either phorbol esters or transforming growth factors to normal cells in culture may induce the appearance of a malignant phenotype. Since the mechanism of transformation by both chemical tumor promoters and growth factors is unknown, it was of interest to investigate whether phorbol esters might potentiate the activity of transforming growth factors. The combination of β-transforming growth factor (β-TGF) and epidermal growth factor (EGF) causes the normally anchorage-dependent cells (NRK-49F) to form colonies in soft agar. In the presence of maximally stimulating concentrations of EGF and suboptimally stimulating concentrations of β-TGF, phorbol 12-myristate-13-acetate (PMA) enhances the soft agar colony growth of NRK-49F cells in a concentration-dependent manner. However, PMA alone or in combination with either EGF or β-TGF does not stimulate soft agar growth. In contrast to the stimulation of PMA, 4α-phorbol 12,13-didecanoate, an inactive phorbol ester, does not potentiate the effects of EGF plus β-TGF on soft agar growth. PMA does not stimulate the growth of NRK-49F cells in monolayer, nor does it further potentiate the monolayer growth induced by EGF with or without β-TGF. Because the addition to NRK-49F cells of compounds which potentiate β-TGF activity increases EGF receptor number, the effects of PMA on the EGF receptor were studied. A short exposure to PMA (30 min) induces a 50{\%} decrease in EGF receptors of NRK cells whether or not they have been exposed to β-TGF. Scatchard analysis shows that this decrease involves primarily high affinity EGF receptors. However, cells treated with PMA for longer periods of time (4, 6, and 24 h) show no change in EGF or β-TGF receptor binding. PMA therefore must potentiate the activity of purified TGFs without causing an increase in EGF or β-TGF receptor binding.",
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