αB-crystallin expression is correlated with phospho-ERK1/2 expression in human breast cancer

人类乳腺癌中 αB-晶体蛋白的表达与磷酸化 ERK1/2 的表达相关

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作者:Chantal van de Schootbrugge, Freekje van Asten, Iris D Nagtegaal, Yvonne M Versleijen-Jonkers, Hanneke W M van Laarhoven, Melissa H Roeffen, Fred C G J Sweep, Johan Bussink, Johannes H A M Kaanders, Ger J M Pruijn, Wilbert C Boelens, Paul N Span

Abstract

αB-crystallin is regarded as a biomarker for triple-negative and/or basal-like breast cancer. In normal breast cells, overexpression of αB-crystallin leads to neoplastic-like changes, which likely relate to enhanced expression of phosphorylated ERK1/2 (pERK1/2). In this study, we investigated whether αB-crystallin expression is correlated to pERK1/2 expression in breast cancer. In a balanced tissue microarray the expression of αB-crystallin and pERK1/2 kinase were determined immunohistochemically, together with the triple-negativity and basal-like markers CK5/6 and SMA and the signaling molecules pAKT, pmTOR, EGFR, and IGF-1R. αB-crystallin expression significantly correlated with triple negativity and basal-like markers CK5/6 and SMA (Pearson Chi-square test p=0.004, p=0.001, and p<0.001, respectively). A significant correlation was also observed with pERK1/2 expression (p=0.002). siRNA-mediated knockdown of αB-crystallin in the triple-negative breast cell line MDA-MB468 did not show an effect on pERK1/2 expression levels, indicating that lowering the level of αB-crystallin does not reduce pERK1/2 expression. Our results confirm that αB-crystallin can be used as a biomarker for triple-negative and/or basal-like breast cancer. The expression of αB-crystallin correlates with pERK1/2 expression in breast cancer tissue suggesting that therapies targeting αB-crystallin might be considered for treatment of triple-negative or basal-like breast cancer.

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