The tyrosine phosphatase DEP-1 induces cytoskeletal rearrangements, aberrant cell-substratum interactions and a reduction in cell proliferation

The receptor protein tyrosine phosphatase density-enhanced phosphatase-1 (DEP-1) has been implicated in aberrant cancer cell growth and immune cell function, however, its function within cells has yet to be properly elucidated. To investigate the cellular function of DEP-1, stable cell lines inducibly expressing DEP-1 were generated. Induction of DEP-1 expression was found to decrease PDGF-stimulated tyrosine phosphorylation of a number of cellular proteins including the PDGF receptor, and to inhibit growth factor-stimulated phosphorylation of components of the MAPK pathway, indicating that DEP-1 antagonised PDGF receptor signalling. This was supported by data showing that DEP-1 expression resulted in a reduction in cell proliferation. DEP-1-expressing cells had fewer actin-containing microfilament bundles, reduced vinculin and paxillin-containing adhesion plaques, and were defective in interactions with fibronectin. Defective cell-substratum adhesion correlated with lack of activation of FAK in DEP-1-expressing cells. Time-lapse interference reflection microscopy of live cells revealed that although small focal contacts at the leading edge were generated in DEP-1-expressing cells, they failed to mature into stable focal adhesions, as found in control cells. Further motility analysis revealed that DEP-1-expressing cells retained limited random motility, but showed no chemotaxis towards a gradient of PDGF. In addition, cell-cell contacts were disrupted, with a change in the localisation of cadherin from discrete areas of cell-cell contact to large areas of membrane interaction, and there was a parallel redistribution of beta-catenin. These results demonstrate that DEP-1 is a negative regulator of cell proliferation, cell-substratum contacts, motility and chemotaxis in fibroblasts.

The effectiveness of an inpatient group cognitive behavioral therapy program for alcohol dependence

The present study evaluated the effectiveness of attendance at a clinically based, short-term, in-patient group CBT program largely based on Monti, Abrams, Kadden, and Cooney(1) to treat problem drinking. Participants were 37 males and 34 females diagnosed with alcohol dependence. Patients attended 42 CBT sessions over three weeks, with each session being one hour in duration. Measures included the Khavari Alcohol Test (KAT), the Short Alcohol Dependence Data Questionnaire (SADD), the Beck Anxiety Index (BAI), the Symptom Checklist-90-Revised (SCL-90), a General Self-Efficacy scale (GSE), and the Drinking Expectancy Profile (DEP). Group attendance rates were monitored daily. Two structured phone calls were conducted at one month and three months post-discharge. Results showed that attendance rates at CBT group sessions were not associated with improvements found at the end of therapy or in drinking behaviors at three-month follow-up. Full support could not be found for the effectiveness of group CBT and cognitive models of problem drinking.