Ultraviolet radiation (UVR) is a known carcinogen participated for the development of skin cancers.,Solar UVR exposure, particularly ultraviolet B (UVB), is the mostly significant environmental risk factor for the occurrence and progress of basal cell carcinoma(BCC).,Both cumulative and intermittent high-grade UVR exposure could promote the uncontrolled replication of skin cells.,There are also exsiting other contributing environmental factors that combine with the UVR exposure to promote the development of BCC.,DNA damage in formation of skin cancers is considered to be a result of UVR toxicity.,It is UVR that could activate a series of oncogenes simultaneously inactivating tumor suppressor genes and aberrant proliferation and survival of keratinocytes that repair these damages.,Furthermore, mounting evidence demonstrates that inflammatory responses of immune cells in the tumor microenvironment plays crucial role in the skin tumorigenesis as well.,In this chapter, we will follow the function of UVR in the onset and development of BCC.,We describe the factors that influence BCC induced by UVR, and also review the recent advances of pathogenesis of BCC induced by UVR from the genetic and inflammatory aspects.
Basal cell carcinoma (BCC) is the most common human cancer, characterized by aberrant activation of the hedgehog (HH) signaling pathway resulting from mutations in the patched 1 (PTCH1) or smoothened (SMO) genes.,In the present study, to uncover the expression profile of HH signaling-related molecules, we thoroughly examined the mRNA and protein expression levels of six molecules including GLI1, GLI2, PTCH1, PTCH2, SHH, and SMO in BCC and various other cutaneous tumors.,Real-time PCR analysis demonstrated that BCC showed remarkably enhanced mRNA expression of all HH molecules, except SMO compared to other skin tumors.,However, immunohistochemical analysis revealed that only GLI1 protein was specifically upregulated in BCC, while the other HH-related proteins did not show any significant differences between the tumors.,Notably, other skin malignancies such as squamous cell carcinoma, sebaceous carcinoma, and malignant melanoma showed no GLI1 expression and there was no difference in GLI1 expression between the BCC subtypes.,In addition, GLI1 and GLI2 expression were strongly associated with the hair follicle stem cell markers, LGR4 and LGR5, which are known target genes of the Wnt pathway.,Our results suggest that GLI1 has the potential to be a diagnostically useful marker for differentiating BCC from other skin malignancies and an interaction between the HH and Wnt signaling pathways may be involved in the development of BCCs.