The transcription factors GLI1 and GLI2 have been implicated in both the initiation and progression of several cancers, including basal cell carcinoma.
Primary human keratinocytes retrovirally expressing GLI1(-) and GLI2(-) showed elevated levels of beta-tubulin III and ARC but not Neurofilament or GAP-43, suggesting that beta-tubulin III and Arc may be early targets of aberrant Gli expression in BCC, whereas expression of Neurofilament and GAP-43 are either later, downstream targets or under control of alternative pathways.
We could now demonstrate that Gli2 gene silencing in BCC tissues made the tumor sensitive to TRAIL (tumor necrosis factor-related apoptosis-inducing ligand)-mediated cell death by downregulating cFlip.
Our results reveal a key role of GLI2 in activation of the activin/BMP antagonist FST in response to HH signaling and provide new evidence for a regulatory interaction between HH and activin/BMP signaling in hair follicle development and BCC.
In order to examine the function of alpha v beta 6, we transfected the transcription factors Gli1 or Gli2 into NTERT, human keratinocytes to generate a BCC model.
There is indication in the literature that preventing Gli2 function may inhibit BCC formation and growth in vivo; however, the mechanism is unclear and difficult to study in humans.
Finally, using in situ hybridization, we show that GLI2 is expressed in the interfollicular epidermis and the outer root sheath of hair follicles in normal skin as well as in BCC tumor islands.
The zinc-finger transcription factor Gli2 has been identified as critical mediator of the Hh signal at the distal end of the pathway, but the molecular mechanisms by which Gli2 regulates cell proliferation or induces epidermal malignancies such as basal cell carcinoma are still unclear.