Molecular mechanism underlying differential apoptosis between human melanoma cell lines UACC903 and UACC903(+6) revealed by mitochondria-focused cDNA microarrays

Apoptosis. 2008 Aug;13(8):993-1004. doi: 10.1007/s10495-008-0231-8.


Human malignant melanoma cell line UACC903 is resistant to apoptosis while chromosome 6-mediated suppressed cell line UACC903(+6) is sensitive. Here, we describe identification of differential molecular pathways underlying this difference. Using our recently developed mitochondria-focused cDNA microarrays, we identified 154 differentially expressed genes including proapoptotic (BAK1 [6p21.3], BCAP31, BNIP1, CASP3, CASP6, FAS, FDX1, FDXR, TNFSF10 and VDAC1) and antiapoptotic (BCL2L1, CLN3 and MCL1) genes. Expression of these pro- and anti-apoptotic genes was higher in UACC903(+6) than in UACC903 before UV treatment and was altered after UV treatment. qRT-PCR and Western blots validated microarray results. Our bioinformatic analysis mapped these genes to differential molecular pathways that predict resistance and sensitivity of UACC903 and UACC903(+6) to apoptosis respectively. The pathways were functionally confirmed by the FAS ligand-induced cell death and by siRNA knockdown of BAK1 protein. These results demonstrated the differential molecular pathways underlying survival and apoptosis of UACC903 and UACC903(+6) cell lines.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics*
  • Apoptosis / radiation effects
  • Apoptosis Regulatory Proteins / genetics*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Cell Survival / radiation effects
  • Computational Biology / methods
  • DNA, Mitochondrial / analysis
  • DNA, Mitochondrial / genetics*
  • DNA, Mitochondrial / radiation effects
  • Fas Ligand Protein / metabolism
  • Fas Ligand Protein / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / genetics*
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Humans
  • Melanoma / genetics*
  • Melanoma / metabolism*
  • Oligonucleotide Array Sequence Analysis / methods*
  • RNA, Small Interfering / genetics
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Signal Transduction / radiation effects
  • Ultraviolet Rays
  • bcl-2 Homologous Antagonist-Killer Protein / genetics
  • bcl-2 Homologous Antagonist-Killer Protein / metabolism


  • Apoptosis Regulatory Proteins
  • BAK1 protein, human
  • DNA, Mitochondrial
  • Fas Ligand Protein
  • RNA, Small Interfering
  • bcl-2 Homologous Antagonist-Killer Protein