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Inhibition of mitogen-induced c-fos expression in melanoma cells by retinoic acid involves the serum response element

K J Busam1, A B Roberts, M B Sporn

  • 1Laboratory of Chemoprevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.

The Journal of Biological Chemistry
|October 5, 1992
PubMed

Insights

All-transretinoic acid (RA) inhibits B16 melanoma cell growth by suppressing proto-oncogene expression. RA specifically targets c-fos transcription via the serum response element (SRE), impacting cell proliferation.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • All-transretinoic acid (RA) is known to affect cell growth.
  • Proto-oncogenes like c-fos and c-jun play roles in cell proliferation and cancer.
  • Understanding RA's mechanism of action is crucial for its therapeutic applications.

Purpose of the Study:

  • To investigate how all-transretinoic acid (RA) inhibits cell growth.
  • To examine the effect of RA on the expression of c-fos and c-jun in B16 melanoma cells.

Main Methods:

  • B16 melanoma cells were treated with varying doses and durations of RA.
  • Proto-oncogene expression (c-fos, c-jun) was measured.
  • Transcriptional inhibition was assessed using promoter constructs containing the serum response element (SRE).

Main Results:

  • RA differentially inhibited proto-oncogene induction by mitogens.
  • Suppression of c-fos occurred at low RA doses (10(-10) M) and short pretreatment (2 h).
  • Inhibition of c-jun required higher RA doses (10(-8) M) and longer pretreatment (>16 h), correlating with decreased cell growth.
  • RA blocked c-fos induction by inhibiting transcription through the SRE.

Conclusions:

  • The serum response element (SRE) is critical for RA-mediated suppression of c-fos transcription.
  • RA's inhibition of c-fos transcription is an early event, while c-jun inhibition and cell growth reduction occur later.
  • These findings elucidate key molecular mechanisms underlying RA's anti-proliferative effects in melanoma.

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