The nucleolar protein dyskerin is involved in the modification of specific uridine residues to pseudouridine on ribosomal and small nuclear RNAs and in the stabilization of the telomerase RNA component (TERC). In this study we investigated for the first time the relationship between dyskerin expression and telomerase activity in a series of 61 primary breast carcinomas. We found that when dyskerin mRNA values were very low the telomerase activity was markedly reduced, independently of the expression of other important components of the telomerase complex such as telomerase reverse transcriptase (TERT). In vitro experiments showed that reduction of dyskerin expression affect telomerase activity through the reduction of TERC. Only when TERC levels were strongly reduced telomerase activity was hindered. Retroviral mediated over-expression of TERC abolished the telomerase impairment due to dyskerin knock down. In conclusion, our results indicated that, beside its effect on ribosome biogenesis, the levels of dyskerin in cancer cells modulate telomerase activity through the regulation of TERC levels, independently of TERT expression. This should be taken into consideration when utilizing TERT expression as a surrogate indicator of telomerase activity in tumour pathology.
Abstract• : This paper analyzes the wage returns from internal migration for recent graduates inItaly. We employ a switching regression model that accounts for the endogeneity of the individual's choice to relocate to get a job after graduation: the omission of this selection decision can lead to biased estimates, as there is potential correlation between earnings and unobserved traits exerting an influence on the decision to migrate. The empirical results sustain the appropriateness of the estimation technique and show that there is a significant pay gap between migrants and nonmigrants; migrants seem to be positively selected and the migration premium is downward biased through OLS estimates. The endogeneity of migration shows up both as a negative intercept effect and as a positive slope effect, the second being larger then the first: bad knowledge of the local labor market and financial constraints lead migrants to accept a low basic wage but, due to relevant returns to their characteristics, they finally obtain an higher wage then the others.
Two cases of alveolar soft part sarcoma have been studied immunocytochemically using antisera against epithelial membrane antigen, lysozyme, keratins, S-100 protein, desmin, vimentin, fetal myosin, slow myosin, alpha-skeletal muscle actin, alpha-smooth muscle actin and myoglobin. The neoplastic cells were negative with all antisera employed with the exception of the alpha-skeletal muscle actin antiserum which stained the cytoplasm of numerous neoplastic elements, including the crystalloid rods, typical cytoplasmic inclusions of these tumours. It is suggested that the presence of this protein indicates rhabdomyoblastic differentiation of these tumours.
Abstract. Lithium is the main therapeutic agent for the treatment of bipolar disorders but nerve cells are not the sole target of this drug. Indeed, lithium has been reported to target numerous cell types and to affect cell proliferation, differentiation and death. Lithium targets a variety of enzymes among which there is GSK-3ß and a number of cell responses elicited by lithium are mediated by the Wnt pathway that is involved in medulloblastoma (MB) pathogenesis. We studied the in vitro effects of lithium on two different MB cell lines: D283MED and DAOY. High doses of lithium inhibited GSK3-ß, decreased cell proliferation and induced nonapoptotic cell death in both cell lines independently by intracellular levels of ß-catenin that is consistently high only in D283MED. At clinical doses, the anti-neoplastic effects were observed only in this cell line, highlighting the importance of a specific molecular background in determining the target therapy response. In conclusion, lithium could be a promising drug in MB, but an accurate molecular profile predictive of drug response still needs to be clarified.
Aims-To investigate whether deletion of the 1p36 region of chromosome 1 is independent of DNA ploidy in breast cancer cells. Methods-Preparations of nuclei from 64 fresh primary breast tumours were studied using dual target fluorescence in situ hybridisation (FISH) combining probes specific for the 1q12 (pUC 1.77) and 1p36 (lp-79)
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