Inhibition of Bcl-xL expression sensitizes normal human keratinocytes and epithelial cells to apoptotic stimuli

Oncogene. 1999 Aug 5;18(31):4495-504. doi: 10.1038/sj.onc.1202836.


The epidermis is continually exposed to harmful mutagens that have the potential to cause DNA damage. To protect the skin from accumulating mutated cells, keratinocytes have developed a highly regulated mechanism of eliminating damaged cells through apoptosis. Bcl-xL is a well-described cell survival protein that when overexpressed in skin can protect keratinocytes from UV radiation-induced apoptosis. To begin to unravel the complex mechanisms that keratinocytes use to survive, we wanted to characterize the role of endogenous Bcl-xL in protecting cells from death. In this study, we describe the development and characterization of an antisense inhibitor to Bcl-xL. We show that this inhibitor reduces Bcl-xL RNA and protein in a concentration-dependent, sequence-specific manner. Furthermore, treatment of keratinocytes and epithelial cells with this inhibitor sensitizes these cells to UV-B radiation and cisplatinum treatment-induced apoptosis. Thus, these results offer direct evidence that Bcl-xL is critical in the protection of skin and epithelial cells from apoptosis and provide a basis for the role of Bcl-xL in keratinocyte and epithelial cell survival.

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Base Sequence
  • Cell Cycle / drug effects
  • Cell Cycle / physiology*
  • Cell Cycle / radiation effects
  • Cells, Cultured
  • Cisplatin / pharmacology
  • Cloning, Molecular
  • Diploidy
  • Epithelial Cells / cytology*
  • Epithelial Cells / drug effects
  • Epithelial Cells / radiation effects
  • HL-60 Cells
  • Humans
  • Keratinocytes / cytology*
  • Keratinocytes / drug effects
  • Keratinocytes / radiation effects
  • Lung Neoplasms
  • Oligonucleotides, Antisense / chemistry
  • Oligonucleotides, Antisense / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / physiology*
  • Skin / cytology
  • Transfection
  • Tumor Cells, Cultured
  • Ultraviolet Rays*
  • bcl-X Protein


  • BCL2L1 protein, human
  • Oligonucleotides, Antisense
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-X Protein
  • Cisplatin