Simultaneous knockdown of BRAF and expression of INK4A in melanoma cells leads to potent growth inhibition and apoptosis

Yanhua Zhao, Yan Zhang, Zhen Yang, Albert Li, Jianli Dong

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Abnormal BRAF and p16INK4A co-exist in 60% of melanomas. BRAF mutation also occurs in 80% of benign nevi where it turns-on p16INK4A resulting in proliferative senescence; loss of p16INK4A removes the inhibitory block leading to melanoma development. Since only melanomas with wild-type BRAF have amplified CDK4 and cyclin D1 genes, p16INK4A-CDK4/6-cyclin D pathway is viewed as linearly downstream of BRAF. Thus, co-occurrence of aberrant BRAF and INK4A may be remnant of changes during melanoma formation without functional significance. To explore this notion, we simultaneously knocked down BRAF (via siRNA) and expressed INK4A cDNA in melanoma cells and observed enhanced growth inhibition. Notably, although each alone had no statistically significant effect on apoptosis, co-expression of BRAF siRNA and INK4A cDNA caused potent apoptosis, which was associated with up-regulation of BIM and down-regulation of BCL2. Our results suggest that aberrant BRAF and INK4A cooperate to promote proliferation and survival of melanoma cells.

Original languageEnglish (US)
Pages (from-to)509-513
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume370
Issue number3
DOIs
StatePublished - Jun 6 2008

Fingerprint

Small Interfering RNA
Melanoma
Complementary DNA
Apoptosis
Cyclin D
Cyclin D1
Growth
Genes
bcl-1 Genes
Nevus
Cell Survival
Up-Regulation
Down-Regulation
Mutation

Keywords

  • Apoptosis
  • BRAF
  • INK4A
  • Melanoma
  • Proliferation

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Simultaneous knockdown of BRAF and expression of INK4A in melanoma cells leads to potent growth inhibition and apoptosis. / Zhao, Yanhua; Zhang, Yan; Yang, Zhen; Li, Albert; Dong, Jianli.

In: Biochemical and Biophysical Research Communications, Vol. 370, No. 3, 06.06.2008, p. 509-513.

Research output: Contribution to journalArticle

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