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Vermeer P.D.,University of South Dakota | Bell M.,University of South Dakota | Lee K.,University of South Dakota | Vermeer D.W.,University of South Dakota | And 8 more authors.
PLoS ONE | Year: 2012

In non-cancerous cells, phosphorylated proteins exist transiently, becoming de-phosphorylated by specific phosphatases that terminate propagation of signaling pathways. In cancers, compromised phosphatase activity and/or expression occur and contribute to tumor phenotype. The non-receptor phosphatase, PTPN13, has recently been dubbed a putative tumor suppressor. It decreased expression in breast cancer correlates with decreased overall survival. Here we show that PTPN13 regulates a new signaling complex in breast cancer consisting of ErbB2, Src, and EphrinB1. To our knowledge, this signaling complex has not been previously described. Co-immunoprecipitation and localization studies demonstrate that EphrinB1, a PTPN13 substrate, interacts with ErbB2. In addition, the oncogenic V660E ErbB2 mutation enhances this interaction, while Src kinase mediates EphrinB1 phosphorylation and subsequent MAP Kinase signaling. Decreased PTPN13 function further enhances signaling. The association of oncogene kinases (ErbB2, Src), a signaling transmembrane ligand (EphrinB1) and a phosphatase tumor suppressor (PTPN13) suggest that EphrinB1 may be a relevant therapeutic target in breast cancers harboring ErbB2-activating mutations and decreased PTPN13 expression. © 2012 Vermeer et al. Source


Landsbergen K.M.,Raboud University Nijmegen Medical Center | Prins J.B.,Raboud University Nijmegen Medical Center | Brunner H.G.,Raboud University Nijmegen Medical Center | Hoogerbrugge N.,Raboud University Nijmegen Medical Center
Familial Cancer | Year: 2011

Current diagnostic practices have shortened the interval between colorectal cancer (CRC) diagnosis and genetic analysis for Lynch syndrome by MSI-testing. We studied the relation of time between MSI-testing since CRC diagnosis (MSI-CRC interval) and psychological distress. We performed a cross-sectional study in 89 patients who had previously been treated for CRC. Data were collected during MSI-testing after genetic counseling. Psychological distress was measured with the IES, the SCL-90 and the POMS; social issues with the ISS, ISB and the ODHCF. The median time of MSI-CRC interval was 24 months (range 0-332), with 23% of the patients diagnosed less than 12 months and 42% more than 36 months prior to MSI-testing. In 34% of the patients cancer specific distress was high (IES scores >26). Mean psychopathology (SCL-90) scores were low, mean mood states (POMS) scores were moderate. Interval MSI-CRC was not related to psychological distress. High cancer specific distress was reported by 24% of patients diagnosed with CRC less than 12 months ago versus 39 and 35% by those diagnosed between 12 and 36 months and more than 36 months ago respectively. Distress was positively related to female gender (P = 0.04), religiousness (P = 0.01), low social support (P = 0.02) and difficulties with family communication (P < 0.001). Shortened time interval between CRC diagnosis and MSI-testing is not associated with higher psychological distress. Females, religious persons, those having low social support and those reporting difficulties communicating hereditary colorectal cancer with relatives are at higher risk for psychological distress. © 2010 The Author(s). Source


Landsbergen K.M.,Raboud University Nijmegen Medical Center | Prins J.B.,Raboud University Nijmegen Medical Center | Kamm Y.J.L.,Raboud University Nijmegen Medical Center | Brunner H.G.,Raboud University Nijmegen Medical Center | Hoogerbrugge N.,Raboud University Nijmegen Medical Center
Familial Cancer | Year: 2010

Women with a BRCA mutation face a complex choice between breast cancer surveillance and prophylactic mastectomy. We determined risk management preferences shortly after genetic test disclosure and mastectomy status after a median observation period of 2 years. The effect of an educational-support group on the realisation of risk management preference was explored. We included 163 newly disclosed BRCA mutation carriers with no history of cancer, whose breast cancer risk management preferences were recorded. All carriers were offered the opportunity to participate an educational-support group. Mastectomy status was checked after a median observation period of 2 years. Of the total sample, 27% had an initial preference for mastectomy and 48% attended an educational-support group. After a median observation period of 2 years, 30% of the total sample had undergone prophylactic mastectomy. Of the women with a preference for surveillance, 90% of educational-support group attendees and 88% of the other mutation carriers, were still under surveillance. The number of women with a preference for mastectomy who actually had a mastectomy performed, was significantly higher in the group that attended an educationalsupport group as compared to those who did not, 89% and 63% respectively (OR 4.8, P = 0.04). Strong predictors for prophylactic mastectomy within 2 years were younger age and prior preference for mastectomy (R2 = 0.57). Nearly all BRCA mutation carriers proceed with their initial choice for surveillance or prophylactic mastectomy. The study provides presumptive evidence that educational-support group participants decide to undergo prophylactic mastectomy earlier than non-attendees. ©Springer Science+Business Media B.V. 2009. Source

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