Análise de genes diferencialmente expressos nas vias de sinalização (Hedgehog e Wnt) em carcinomas basocelulares humanos

AUTOR(ES)
FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

16/04/2012

RESUMO

Hedgehog (HH) and Wingless-Int (Wnt) signaling pathway are related to the process of cellular proliferation, differentiation, angiogenesis, matrix remodeling and homeostasis of stem cells. Over the years, several mutations in HH signaling pathway have been identified, including the loss of function mutations in ptch1 and the gain of function mutations in smo. Basal cell carcinoma (BCC) is the most common cancer and has multifactorial risks. Nevertheless, it is still not possible to associate the activation of HH signaling pathway for BCCs different histological subtypes. As tumor progression is a multistep process, the study of genes related to those pathways will allow a better understanding of BCCs carcinogenesis. In this context, the objective of this work was to analyze differential genes expression in HH and Wnt signaling pathway in patients with superficial and nodular basal cell carcinoma compared between them and with a normal skin tissue. The samples were collect from surgery at the center of Dermatology at Hospital Regional da Asa Norte. Firstly, it was necessary standardize RNA extraction. The weight of the samples was less than 0,03g and the techniques described for the extraction were not efficient to obtaining a good RNA. Gene expression analysis was done by 84 genes that were selected and validate by PCR Array. From those, 36 genes showed differential gene expression when it was compared the 3 groups. For the statistic analysis were considered p-value, correlation method and fold regulation. Comparing nodular BCC to superficial BCC, 8 genes (bmp5, hhip, otx2, prky, ptch1, ptch2, wnt2, zic1) were upregulated and 9 genes (csnk1a1l, dhh, ihh, ptchd2, wnt16, wnt3a, wnt7a, wnt8a, wnt9b) were downregulated; comparing nodular BCC to control without cancer, 8 genes (foxe1, c6orf138, hhip, lrp2, otx2, prky, ptch1, ptch2) were upregulated and 26 genes (bmp2, bmp4, cdon, csnk1a1l, dhh, erbb4, fgfr3, ihh, kctd11, ptchd1, ptchd2, shh, wif1, wnt10a, wnt10b, wnt16, wnt2b, wnt3, wnt3a, wnt4, wnt7a, wnt8a, wnt9b, zic2) were downregulated; and comparing superficial BCC to control without cancer, 3 genes (foxe1, lrp2, ptch2) were upregulated and 14 genes (bmp2, bmp4, bmp5, cdon, erbb4, fgfr3,wif1, wnt10a, wnt16, wnt2, wnt2b, wnt3, wnt4, wnt7b) were downregulated. After these findings, a graphic representation localizing and inferring a possible regulation of the differential gene expression was made. The data reinforces literature of basal cell carcinoma and its subtypes and corroborate it. Studies on genetic alterations involved in tumorigenesis are important for the molecular characterization of a tumor. It may provide useful tools for the development and the identification of molecular markers aimed at Hedgehog and Wnt signaling pathways.

ASSUNTO(S)

pele câncer genes biotecnologia genetica nodular basal cell carcinoma superficial basal cell carcinoma hedgehog signalling pathway wnt signalling pathway pcr array

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