Expression of periostin in human breast cancer

Abstract

Aims: Periostin is a secreted adhesion protein, normally expressed in mesenchime-derived cells. Aberrant expression of the periostin gene in epithelial tumors seems to play a role in angiogenesis and metastases. Aim of the study was to investigate periostin expression in a consecutive series of breast carcinomas and correlated it with established biological and prognostic factors. Method: A consecutive series of 206 breast carcinomas was investigated by immunohistochemistry with a specific antiperiostin antibody. We also analyzed immunohistochemical expression of estrogen and progesterone receptors, Ki-67 (MIB-1), HER-2/neu, VEGF-A, VEGFR-1 and VEGFR-2. Periostin expression was also investigated in MCF-7 and MDA-468 cell lines by immunohistochemistry, Western blot and quantitative RT-PCR. Localization of periostin was investigate in MCF-7 cells by the GFP approach. Results: Periostin was found to be highly expressed in carcinoma cells, but not in normal breast tissues. The pattern of expression was mainly cytoplasmic. However, in 12% of cases a nuclear reactivity was observed. Nuclear periostin significantly correlated with tumor size, and with expression of estrogen receptor, progesterone receptor, VEGF-A, VEGFR-1 and VEGFR-2. A nuclear localization of periostin was also observed in MCF-7 and MDA-468 cell lines. In MCF-7 cells the nuclear localization of periostin was also demonstrated by tranfection of a vector expressing a GFP-periostin chimeric protein. Conclusions: Our results indicate that the aberrant gene expression of periostin in breast cancer cells is associated to an abnormal nuclear localization of the protein. The nuclear localization of periostin in breast cancer may induce significant biological effects.