Involvement of retinoblastoma tumour-suppressor protein in mineral lung exposition

Recently studies have demonstrated a correlation between mesothelioma and fluoro-edenite fibers exposition. These fibers very similar to the asbestos one’s induce functional modifications and biological cyto- and genotoxicity but the molecular mechanism involved in cells malignant transformations are still largely unknown.It has been shown recently that high level expression of the RB-family proteins as well as p53 have been detected in human mesothelioma.Retinoblastoma protein (RB) is a 928-amino acid nuclear phosphoprotein that plays a central role in the control of the cell cycle, cellular growth regulation, differentiation and apoptosis. pRB functions as a checkpoint during the G1 phase of the cell cycle; it is also involved in preventing cells from undergoing apoptosis. Phosphorylation of RB results in a consequent loss of its ability to inhibit cell cycle progression and S phase entry. Dephosphorylation of RB not only promotes cell cycle arrest and a return to the G1 phase, but also appears to be a key event in most instances of apoptosis. In this study, we investigated for the first time in an “in vivo” sheep model the immunohistochemical expression of RB and pRB in lung tissues exposed to fluoro-edenite fibers.The results showed an increased immunoexpression of pRB both in the alveolar epithelium and in the interstitium, above all localized in close contact to fluoro-edenite fibers. RB immunostaining was instead quite reduced or completely absent. Overexpression of pRB, therefore, suggested to be a programmed protective response of fluoro-edenite exposed lung, to uncontrolled proliferation.