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Interdependence between cell adhesion and proliferation in normal and neoplastic cells

Objective



We plan to analyze the reciprocal interactions existing between cell adhesion and proliferation. These interactions are suggested by phenomena such as the "anchorage dependence" for G1 to S transition in the cell cycle and "contact inhibition", which are commonly dysregulated in cancer cells. We will analyze in vitro models represented by normal, pre-transformed or neoplastic cells, arrested in GO/G1 by starvation and contact inhibition and subsequently stimulated by adhesion to matrix or specifc antibodies or kept in a non adherent state. Transcripts whose levels are selectively controlled by any of the aforementioned conditions will be differentially analyzed using the "Differential Display of RT-PCR products" (DDRT-PCR) approach, and subsequently cloned for complete characterization. The role of functional cyclin/cyclin-dependent kinase(CDK)/ cyclin inhibitor (CKI) complexes in affecting the adhesive phenotype will be explored at the biochemical and functional level, using synchronized cell populations at defined stages in the cell cycle. The long term goal of the project is to identify early mutational events affecting genes whose expression controls the interdependent functions of adhesion and growth reponse, and whose alterations correlate with tumor progression.

Funding Scheme

RGI - Research grants (individual fellowships)

Coordinator

Fondazione Centro San Raffaele del Monte Tabor - Istituto di Ricovero e Cura a Carattere Scientifico
Address
Via Olgettina 60
20132 Milano
Italy

Participants (1)

Not available
Germany