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Expression of the GLI2 oncogene and its isoforms in human basal cell carcinoma
M Tojo1, H Kiyosawa, K Iwatsuki
1Department of Dermatology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima 960-1295, Japan.
Background:
Mutations of the patched (Ptc) gene, a developmental regulator implicated in the signalling pathway via sonic hedgehog (Shh) and smoothened (Smo), play an essential pathogenic role in the development of basal cell carcinomas (BCCs). We previously reported the upregulation of Shh signal transducers, including Ptc, Smo and hedgehog-interacting protein, in BCCs. In vertebrates, specific downstream effectors in the Shh signalling pathway include three zinc-finger transcription factors, Gli1, Gli2 and Gli3. Gli1 possesses only an activation domain, while Gli2 and Gli3 contain both activation and repression domains. It remains unclear which of these transcription factors are responsible for the development of BCCs.
Objectives:
To examine the expression pattern of Gli2 mRNA by human BCCs in comparison with those by normal human skin and various skin tumours.
Methods:
We performed quantitative reverse transcriptase-polymerase chain reaction analyses with a series of samples from BCCs, other skin tumours and normal skin.
Results:
We found that Gli2 mRNA expression was enhanced in the BCCs we examined, whereas there was no significant increase in other skin tumours or normal skin. Of four spliced Gli2 isoforms designated Gli2alpha, beta, gamma and delta, the expression of Gli2beta mRNA was increased the most in BCCs.
Conclusions:
As Gli2beta is an isoform spliced at the first splicing site containing a repression domain and consists of an intact activation domain, its overexpression may lead to the upregulation of the Shh signalling pathway, thereby inducing BCCs.
Insights
Overexpression of Gli2beta mRNA in basal cell carcinomas (BCCs) may drive tumor development by upregulating the sonic hedgehog (Shh) pathway. This study highlights Gli2beta as a key factor in BCC pathogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Dermatology
Background:
- Basal cell carcinomas (BCCs) are linked to mutations in the patched (Ptc) gene and dysregulation of the sonic hedgehog (Shh) signaling pathway.
- Previous research indicated upregulation of Shh pathway components like Ptc and Smo in BCCs.
- The roles of downstream transcription factors Gli1, Gli2, and Gli3 in BCC development remain unclear.
Purpose of the Study:
- To investigate the expression patterns of Gli2 mRNA in human BCCs.
- To compare Gli2 mRNA expression in BCCs with normal skin and other skin tumors.
- To identify specific Gli2 isoforms involved in BCC pathogenesis.
Main Methods:
- Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was employed.
- Analysis was conducted on samples from BCCs, various skin tumors, and normal skin.
Main Results:
- Gli2 mRNA expression was significantly elevated in BCCs compared to normal skin and other skin tumors.
- Among the four identified Gli2 isoforms (Gli2alpha, beta, gamma, delta), Gli2beta mRNA showed the most pronounced increase in BCCs.
- No significant increase in Gli2 mRNA was observed in non-BCC skin tumors or normal skin samples.
Conclusions:
- Overexpression of Gli2beta, an isoform with both activation and repression domains, is implicated in BCC development.
- The enhanced expression of Gli2beta may lead to the upregulation of the Shh signaling pathway, driving BCC formation.
- Gli2beta represents a potential therapeutic target for basal cell carcinomas.