Abstract
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.
Highlights
Basal cell carcinoma (BCC) is the most common human cancer, and approximately 750, 000 basal cell carcinomas (BCCs) are diagnosed each year in the United States alone [1]
Real-time PCR results demonstrated that all HH-related molecules, except SMO, were remarkably elevated in BCC compared to normal skin and most other skin tumors (Fig 1)
Out of the nine skin tumors examined, only BCCs exhibited substantially elevated levels of all the HH-related molecules, except SMO. This finding is consistent with previous studies reporting that HH signaling can activate genes involved in positive and negative feedback such as GLI1, GLI2, patched 1 (PTCH1), and PTCH2 [21,22,23]
Summary
Basal cell carcinoma (BCC) is the most common human cancer, and approximately 750, 000 BCCs are diagnosed each year in the United States alone [1]. BCCs are largely caused by exposure to ultraviolet light and develop on the sun-exposed areas of skin. They are classically slow-growing and locally invasive cancers that are considered to arise from hair follicles [2, 3]. The majority of BCCs occur sporadically, basal cell nevus syndrome Hedgehog signaling molecules in basal cell carcinomas. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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