Is the small heat shock protein αB-crystallin an oncogene?
J. Clin. Invest. Sofia K. Gruvberger Saal , et al. 116:30 doi:10.1172/JCI27462 [Go to this article.]

Figure 1
αB-Crystallin overexpression causes neoplastic-like transformation of human mammary epithelial cells. 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.