Résumé :
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Communication n° 163 The Dp71 associated protein complex (Dp71~DAPC) has been implicated in cell adhesion, differentiation and embryonic development. Moreover, the DAPC members, who connect the extracellular matrix to the cytoskeleton, a- and b-dystroglycan, have been found diminished in carcinomas of epithelial origin. However, it remains unknown whether the DAPC and the cytoskeleton are altered during carcinogenesis. Our goal was to study the Dp71~DAPC, b1-integrin and cytoskeleton protein expression in hepatic preneoplastic nodules (PN) and hepatocellular carcinomas (HCC) induced in rats. The protein pattern of Dp71 isoforms (Dp71s) and DAP were determined by Western-blot and the complex was characterized by immunoprecipitation. Several Dp71s were found in plasma membrane and nuclei fractions. The Dp71~DAPC, was composed by four Dp71s (74-76 kDa) and one of 55 kDa, associated with b-dystroglycan, a- and g-syntrophins, b-dystrobrevin and also with actin. During hepatocarcinogenesis, some Dp71s, DAP, b1-integrin, actin and b-tubulin were more concentrated in the PN stage in relation to normal tissue. In contrast, in HCC, the protein level of b-dystroglycan, b-dystrobrevin, b1-integrin and b-tubulin was diminished whereas some Dp71s, a- and b-syntrophins were normal and g-syntrophin was increased. The dystroglycan, Dp71 and b-actin transcription, analyzed by RT-PCR, was not correlated with the corresponding protein expression in HCC. We showed that the Dp71~DAPC is disrupted during experimental HCC progression, confirming that dystroglycan is a histological diagnostic negative marker for neoplastic lesions and b-dystrobrevin may be a bivalent marker for PN and HCC. In conclusion, the disruption of Dp71~DAPC like b1-integrin and cytoskeleton could be implicated in carcinogenesis.
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