αB-Crystallin is a Novel Oncoprotein Associated with Poor Prognosis in Breast Cancer

Abstract

PurposeαB-crystallin, a small heat shock protein, is an anti-apoptotic protein associated with aggressive tumor behavior. A recent study revealed that αB-crystallin is overexpressed in a metastatic variant of the GI101A human breast carcinoma cell line. The purpose of this study was to investigate whether αB-crystallin is related to other breast tumor markers and can predict a breast cancer prognosis.MethodsEighty-two patients who underwent breast cancer surgery at Hallym Sacred Heart Hospital were enrolled. αB-crystallin expression was determined by immunohistochemical staining. Estrogen receptor, progesterone receptor (PR), human epidermal growth factor receptor, lymphovascular invasion, histological grade, other tumor markers and time to recurrence were compared with αB-crystallin expression.ResultsαB-crystallin expression in breast cancer tissues was associated with PR (p=0.030), the number of metastatic lymph nodes (pN) (p=0.020), lymphovascular invasion (p=0.022), histological grade (p=0.004) and triple negative breast cancer (TNBC) (p=0.004). αB-crystallin expression significantly decreased time to recurrence (p=0.039).ConclusionThe results revealed a strong relationship between αB-crystallin and poor prognostic factors such as the number of metastatic lymph nodes (especially pN2), TNBC, and rapid time to recurrence. We believe that αB-crystallin could be a novel oncoprotein biomarker of a poor prognosis in breast cancer.

Chronic Inflammation in Cancer Development

“…A promising approach in cancer therapy also might be targeting HSP, because up-regulated Hsp90 and Hsp70 in cancer cells have been recognized as important drug targets and are under intensive studies in recent years. HSP are currently being targeted in the therapy of breast cancer and other carcinomas and effective drugs for Hsp90 (e.g., geldanamycin and its analogs) have been synthesized and evaluated in clinical trials (Calderwood and Gong, 2011; Kim and Kim, 2011). HSP vaccines have been intensively studied in the preceding two decades, proving to be safe and effective in treating a number of malignancies (Murshid et al, 2011).…”

αB-Crystallin promotes oncogenic transformation and inhibits caspase activation in cells primed for apoptosis by Rb inactivation

“…We recently reported that αB-crystallin is expressed in about half of basal-like breast tumors and promotes an invasive, apoptosis-resistant phenotype in breast epithelial cells [18]. Others have confirmed the association of αB-crystallin expression with poor outcomes and the basal-like/triple-negative subtype of breast cancer and described a similar oncogenic role for αB-crystallin in the pathogenesis of glioblastoma multiforme [16, 35, 36]. It is tempting to speculate that the observed role of αB-crystallin in suppressing caspase activation in setting of Rb inactivation and p53 inhibition might account for the frequent occurrence of these three molecular events ( Rb loss, TP53 mutation, and αB-crystallin expression) in clinically aggressive triple-negative breast cancers, although it remains to be determined how frequently all three of these events occur in individual basal-like/triple-negative tumors.…”

αB-crystallin: Portrait of a malignant chaperone as a cancer therapeutic target

“…Multiple studies have confirmed the association of αB-crystallin protein expression with expression of basal markers ( e.g. , cytokeratin 5 and 14) and TNBC, which is associated with poor survival due to early relapse in the lungs and brain (Moyano et al, 2006; Ivanov et al, 2008; Smid et al, 2008; Kennecke et al, 2010; Kim et al, 2011; Toft & Cryns, 2011; Tsang et al, 2012; Malin et al, 2014). αB-crystallin is also commonly expressed in metaplastic carcinomas, a rare histologic subtype with spindle or sarcomatoid features that express basal markers and are likely to represent a distinctive subset of basal-like breast tumors (Reis-Filho et al, 2006; Sitterding et al, 2008; Chan et al, 2011).…”

“…αB-crystallin is abundantly expressed in a multitude of solid tumors, including malignant glioblastomas, osteosarcoma, retinoblastoma and carcinomas of the breast, prostate, ovary, colon, liver, lung (non-small cell), head and neck, and thyroid (Aoyama et al, 1993; Wulfkuhle et al, 2002; Stronach et al, 2003; Chelouche-Lev et al, 2004; Shi et al, 2004, 2014; Chin et al, 2005; Moyano et al, 2006; Goplen et al, 2010; Kim et al, 2011; Mao et al, 2012; Huang et al, 2013; Volkmann et al, 2013; Davidov et al, 2014; Qin et al, 2014; Yilmaz et al, 2015). In many cases, αB-crystallin levels are higher in the tumor tissue than the surrounding non-tumor tissue (Wulfkuhle et al, 2002; Shi et al, 2004, 2014; Mao et al, 2012; Qin et al, 2014; Yilmaz et al, 2015).…”