Is the small heat shock protein αB-crystallin an oncogene?
Sofia K. Gruvberger Saal, Ramon Parsons
Sofia K. Gruvberger Saal, Ramon Parsons
Published January 4, 2006
Citation Information: J Clin Invest. 2006;116(1):30-32. https://doi.org/10.1172/JCI27462.
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Commentary

Is the small heat shock protein αB-crystallin an oncogene?

Abstract

In the last 5 years, global gene expression profiling has allowed for the subclassification of the heterogeneous disease of breast cancer into new subgroups with prognostic significance. However, for most subgroups, the nature of the contributions of individual genes to the clinical phenotypes remains largely unknown. In this issue of the JCI, Moyano and colleagues further examine the oncogenic potential of the small heat shock protein α-basic–crystallin, commonly expressed in tumors of the basal-like breast cancer subtype associated with poor prognosis, and show that it is an oncogenic protein in the breast.

Authors

Sofia K. Gruvberger Saal , Ramon Parsons

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Figure 1

αB-Crystallin overexpression causes neoplastic-like transformation of human mammary epithelial cells.

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αB-Crystallin overexpression causes neoplastic-like transformation of hu...
MCF-10A, immortalized human mammary epithelial cells, form acinar-like structures consisting of a single layer of polarized cells surrounding a hollow lumen, resembling normal breast ducts, when grown in 3D basement membrane culture. Activation of oncogenes such as ErbB2 induces neoplastic-like changes in these mammary acini. In this issue of the JCI, Moyano et al. (9) demonstrate that MCF-10A cells stably overexpressing WT αB-crystallin (αB-WT) form large, abnormal acini with filled lumen in contrast to the normal acini formed by empty vector–infected control cells (pLXSN) and cells overexpressing a pseudophosphorylation mutant of αB-crystallin (αB-3XSE). Immunostained cross sections of the acini displayed higher levels of αB-crystallin (green) in αB-WT acini and marked disruption of normal acinar polarity, as evidenced by the localization pattern of the apical marker GM130 (red; upper panels) and the basolateral marker integrin β4 (red; lower panels), compared with pLXSN and αB-3XSE cells. In addition, the dramatic loss of polarity and disruption of acinar morphology in αB-crystallin–overexpressing MCF-10A cells were also accompanied by increased EGF- and anchorage-independent growth, increased proliferation, diminished apoptosis, and increased migration and invasion, and these cells formed tumors in nude mice. These findings clearly indicate that αB-crystallin is an oncogenic protein in human mammary epithelial cells.