The shift in ocular dominance induced by brief monocular deprivation is greatest during a postnatal critical period and is thought to decline irreversibly thereafter. However, here we demonstrate that complete visual deprivation through dark exposure restores rapid ocular dominance plasticity in adult rats. In addition, the loss of visual acuity resulting from chronic monocular deprivation is reversed if dark exposure precedes removal of the occlusion in adulthood, suggesting a potential use for dark exposure in the treatment of adult amblyopia.

Phosphoinositide 3-OH kinases (PI3Ks) are a group of major intracellular signaling molecules. In our previous study, we found that inhibition of PI3K activity suppressed the androgen receptor (AR)-mediated gene expression in prostate cancer cells. The AR has been considered as a critical determinant for the development and progression of human prostate cancers. In this study, we sought to identify the PI3K isoforms involved in AR transactivation. Using a gene-specific small interference RNA (siRNA) approach, we determined that the regulatory isoform p85a and the catalytic isoform p110b, but not p110a, were required for androgen-stimulated AR transactivation and cell proliferation in prostate cancer cells. Consistently, overexpression of wild-type p110b but not p110a gene led to androgen-independent AR transactivation. Silencing p110b gene in prostate cancer cells abolished tumor growth in nude mice. Of the dual (lipid and protein) kinase activities, p110b's lipid kinase activity was required for AR transactivation. Further analysis by a chromatin immunoprecipitation assay showed that p110b is indispensable for androgen-induced AR-DNA interaction. Finally, gene expression analysis of clinical specimens showed that both p85a and p110b were highly expressed in malignant prostate tissues compared to the nonmalignant compartments, and their expression levels correlated significantly with disease progression. Taken together, our data demonstrated that p85a and p110b are essential for androgen-stimulated AR transactivation, and their aberrant expression or activation might play an important role in prostate cancer progression.

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