Overexpression of platelet-derived growth factor receptor a in breast cancer is associated with tumour progression

• Tipo: Artigo em Revista Científica Internacional
• Data: 2005

Autores

Carvalho, I (Autor) Outra; Milanezi, F (Autor) Outra; Martins, A (Autor) Outra; Reis, RM (Autor) Outra; Fernando Schmitt (Autor) FMUP

Revista

Título: Breast Cancer Research

Vol. 7

Páginas: R788-R795

ISSN: 1465-5411

Editora: Springer Nature

Indexação

ISI Web of Knowledge - 169 Citações

Scopus - 181 Citações

Outras Informações

ID Authenticus: P-000-59R

DOI: 10.1186/bcr1304

Abstract (EN): Introduction Receptor tyrosine kinases have been extensively studied owing to their frequently abnormal activation in the development and progression of human cancers. Platelet-derived growth factor receptors (PDGFRs) are receptors with intrinsic tyrosine kinase activity that regulate several functions in normal cells and are widely expressed in a variety of malignancies. After the demonstration that gastrointestinal stromal tumours without c-Kit mutations harbour PDGFR-alpha-activating mutations and that PDGFR-alpha is also a therapeutic target for imatinib mesylate, the interest for this receptor has increased considerably. Because breast cancer is one of the most frequent neoplasias in women worldwide, and only one study has reported PDGFR-alpha expression in breast carcinomas, the aim of this work was to investigate the potential significance of PDGFR-alpha expression in invasive mammary carcinomas. Methods We used immunohistochemistry to detect PDGFR-alpha overexpression on a series of 181 formalin-fixed paraffin-embedded invasive ductal breast carcinomas and in two breast cancer cell lines: MCF-7 and HS578T. We associated its expression with known prognostic factors and we also performed polymerase chain reaction - single-stranded conformational polymorphism and direct sequencing to screen for PDGFR-alpha mutations. Results PDGFR-alpha expression was observed in 39.2% of the breast carcinomas and showed an association with lymph node metastasis ( P = 0.0079), HER-2 expression ( P = 0.0265) and Bcl2 expression ( P = 0.0121). A correlation was also found with the expression of platelet-derived growth factor A ( PDGF-A; P = 0.0194). The two cell lines tested did not express PDGFR-alpha. Screening for mutations revealed alterations in the PDGFR-alpha gene at the following locations: 2500A-->G, 2529T-->A and 2472C-->T in exon 18 and 1701G-->A in exon 12. We also found an intronic insertion IVS17-50insA at exon 18 in all sequenced cases. None of these genetic alterations was correlated with PDGFR-alpha expression. The cell lines did not reveal any alterations in the PDGFR-alpha gene sequence. Conclusion PDGFR-alpha is expressed in invasive breast carcinomas and is associated with biological aggressiveness. The genetic alterations described were not correlated with protein expression, but other mechanisms such as gene amplification or constitutive activation of a signalling pathway inducing this receptor could still sustain PDGFR-alpha as a potential therapeutic target.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 8