Targeted disruption of Bcl-xL in mouse keratinocytes inhibits both UVB- and chemically induced skin carcinogenesis

Joon Kim Dae, Ken Kataoka, Shigetoshi Sano, Kevin Connolly, Kaoru Kiguchi, John DiGiovanni

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Bcl-xL is one of several antiapoptotic proteins regulated by signal transducer and activator of transcription 3 (Stat3). We have recently shown that Stat3 is required for chemically induced and ultraviolet B (UVB)-induced skin carcinogenesis. In this study, the functional role of Bcl-xL in skin carcinogenesis was investigated using skin-specific Bcl-xL-deficientmice. In thismodel, Bcl-xL expression is disrupted in the basal compartment ofmouse epidermis using the bovine keratin 5 (K5) promoter to drive expression of Cre recombinase (K5.Cre × Bcl-x L fl/fl mice). A significant increase in apoptosis induced by either UVB irradiation or 7,12-dimethylbenz[a]anthracene (DMBA) treatment was observed in the epidermis of BclxL-deficient mice. Furthermore, an increase in apoptotic cells was noted in hair follicle keratinocytes, including those located in the bulge region. Cell proliferation was not affected by Bcl-xL deficiency following exposure to either UVB or 12-O-tetradecanoylphorbol-13-acetate (TPA). Bcl-xL-deficient mice were more resistant than wild-type controls to skin tumor development with delayed onset and reduced number of tumors using either UVB or the DMBA/TPA two-stage regimen. Moreover, Bcl-2,Mcl-1, and survivin protein levelswere increased in the epidermis of Bcl-xL-deficientmice in the absence of stimuli. Furthermore, levels of these antiapoptotic proteinswere also high in skin tumors fromBcl-xL-deficient mice that developed in response to either UVB or two-stage carcinogenesis protocols. Collectively, these studies demonstrate that Bcl-xL plays a role early in skin carcinogenesis through its anti-apoptotic functions to enhance survival of keratinocytes, including bulge region keratinocyte stem cells, following DNA damage.

Original languageEnglish (US)
Pages (from-to)873-885
Number of pages13
JournalMolecular Carcinogenesis
Issue number10
StatePublished - Oct 2009
Externally publishedYes


  • Apoptosis
  • DMBA
  • TPA
  • UVB

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research


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