Oncogenic mechanisms of HOXB13 missense mutations in prostate carcinogenesis

• Tipo: Artigo em Revista Científica Internacional
• Data: 2016

Autores

Cardoso, M (Autor) Outra; Maia, S (Autor) Outra; Paulo, P (Autor) Outra; Manuel R Teixeira (Autor) ICBAS

Revista

Título: Oncoscience

Vol. 3

Páginas: 288-296

ISSN: 2331-4737

Editora: Impact Journals

Indexação

Scopus - 7 Citações

Outras Informações

ID Authenticus: P-00S-M2A

DOI: 10.18632/oncoscience.322

Abstract (EN): The recurrent germline mutation HOXB13 p.(Gly84Glu) (G84E) has recently been identified as a risk factor for prostate cancer. In a recent study, we have performed full sequencing of the HOXB13 gene in 462 Portuguese prostate cancer patients with early-onset and/or familial/hereditary disease, and identified two novel missense mutations, p.(Ala128Asp) (A128D) and p.(Phe240Leu) (F240L), that were predicted to be damaging to protein function. In the present work we aimed to investigate the potential oncogenic role of these mutations, comparing to that of the recurrent G84E mutation and wild-type HOXB13. We induced site-directed mutagenesis in a HOXB13 expression vector and established in vitro cell models of prostate carcinogenesis with stable overexpression of either the wild-type or the mutated HOXB13 variants. By performing in vitro assays we observed that, while the wild-type promotes proliferation, also observed with the F240L variant along with a decrease in apoptosis, the A128D mutation decreases apoptosis and promotes anchorage independent growth. No phenotypic impact was observed for the G84E mutation in the cell line model used. Our data show that specific HOXB13 mutations are involved in the acquisition of different cancer-associated capabilities and further support an oncogenic role for HOXB13 in prostate carcinogenesis.

Idioma: Inglês

Tipo (Avaliação Docente): Científica