Differential Roles of Fibroblast Growth Factor Receptors (FGFR) 1, 2 and 3 in the Regulation of S115 Breast Cancer Cell Growth

Fibroblast growth factors (FGFs) regulate the growth and progression of breast cancer. FGF signaling is transduced through FGF receptors 1-4, which have oncogenic or anti-oncogenic roles depending on the ligand and the cellular context. Our aim was to clarify the roles of FGFR1-3 in breast cancer cell growth in vitro and in vivo. Pools of S115 mouse breast cancer cells expressing shRNA against FGFR1, 2 and 3 were created by lentiviral gene transfer, resulting in cells with downregulated expression of FGFR1, FGFR2 or FGFR3 (shR1, shR2 and shR3 cells, respectively) and shLacZ controls. FGFR1-silenced shR1 cells formed small, poorly vascularized tumors in nude mice. Silencing of FGFR2 in shR2 cells was associated with strong upregulation of FGFR1 expression and the formation of large, highly vascularized tumors compared to the control tumors. Silencing FGFR3 did not affect cell survival or tumor growth. Overexpressing FGFR2 in control cells did not affect FGFR1 expression, suggesting that high FGFR1 expression in shR2 cells and tumors was associated with FGFR2 silencing by indirect mechanisms. The expression of FGFR1 was, however, increased by the addition of FGF-8 to starved shLacZ or MCF-7 cells and decreased by the FGFR inhibitor PD173074 in shR2 cells with an elevated FGFR1 level. In conclusion, our results demonstrate that FGFR1 is crucial for S115 breast cancer cell proliferation and tumor growth and angiogenesis, whereas FGFR2 and FGFR3 are less critical for the growth of these cells. The results also suggest that the expression of FGFR1 itself is regulated by FGF-8 and FGF signaling, which may be of importance in breast tumors expressing FGFs at a high level

Seasonal Changes in Mood and Behavior Are Linked to Metabolic Syndrome

BACKGROUND: Obesity is a major public health problem worldwide. Metabolic syndrome is a risk factor to the cardiovascular diseases. It has been reported that disruptions of the circadian clockwork are associated with and may predispose to metabolic syndrome. METHODOLOGY AND PRINCIPAL FINDINGS: 8028 individuals attended a nationwide health examination survey in Finland. Data were collected with a face-to-face interview at home and during an individual health status examination. The waist circumference, height, weight and blood pressure were measured and samples were taken for laboratory tests. Participants were assessed using the ATP-III criteria for metabolic syndrome and with the Seasonal Pattern Assessment Questionnaire for their seasonal changes in mood and behavior. Seasonal changes in weight in particular were a risk factor of metabolic syndrome, after controlling for a number of known risk and potential confounding factors. CONCLUSIONS AND SIGNIFICANCE: Metabolic syndrome is associated with high global scores on the seasonal changes in mood and behavior, and with those in weight in particular. Assessment of these changes may serve as a useful indicator of metabolic syndrome, because of easy assessment. Abnormalities in the circadian clockwork which links seasonal fluctuations to metabolic cycles may predispose to seasonal changes in weight and to metabolic syndrome

The relationship between mood and sleep in different female reproductive states

Peer reviewe

Measurement errors in multivariate measurement scales

Our aim is to construct a general measurement framework for analyzing the effects of measurement errors in multivariate measurement scales. We define a measurement model, which forms the core of the framework. The measurement scales in turn are often produced by methods of multivariate statistical analysis. As a central element of the framework, we introduce a new, general method of estimating the reliability of measurement scales. It is more appropriate than the classical procedures, especially in the context of multivariate analyses. The framework provides methods for various topics related to the quality of measurement, such as assessing the structural validity of the measurement model, estimating the standard errors of measurement, and correcting the predictive validity of a measurement scale for attenuation. A proper estimate of reliability is a requisite in each task. We illustrate the idea of the measurement framework with an example based on real data.Measurement error Measurement scale Factor analysis Reliability Validity

A new measure for dispositional optimism and pessimism in young children

Lemola S, Räikkönen K, Matthews KA, et al. A new measure for dispositional optimism and pessimism in young children. European Journal of Personality. 2010;24(1):71-84.We describe here a new test for dispositional optimism and pessimism in young children, the Parent‐rated Life Orientation Test of children (the PLOT) and assess its psychometric properties. Two hundred and twenty one mother–father pairs rated their children's (mean age = 8.1, SD = 0.3 years) dispositional optimism and pessimism using a new scale, the PLOT, including four optimism and four pessimism items. We associated the PLOT with parent‐rated self‐esteem (Behavioral Rating Scale of Presented Self‐Esteem in Young Children), social competence (Social Competence and Behaviour Evaluation Scale, the SCBE‐30), psychiatric symptoms (Child Behaviour Checklist, the CBCL) and temperament (Children's Behaviour Questionnaire, the CBQ) of the child. A confirmatory factor analysis (CFA) of the mother‐ and father‐rated PLOT revealed a significantly better fit for a two‐ over a one‐factor solution (p < 0.001). The optimism and pessimism subscales displayed good reliabilities, inter‐parental agreement and modest to moderate associations, in the expected direction, with the measures of self‐esteem, social competence, temperament and behaviour problems. To conclude, the PLOT shows good construct and convergent validity and reliability. The findings encourage its use to assess early emerging generalized expectancies of positive and negative outcomes in young children. Copyright © 2009 John Wiley & Sons, Ltd

FGF-induced ERK1/2 activation in sh cells.

<p>Cells were pre-cultured in DC-FBS for 48 h and then treated with A) 25 ng/ml FGF-8b, B) 10 ng/ml FGF-2 or 100 ng/ml FGF-7 or PBS vehicle for indicated time periods. Whole-cell lysates were generated from cells and protein was subjected to SDS-PAGE and immunoblotted with antibodies against p-ERK1/2 and ERK1/2. The intensity of the bands was determined by scanning densitometry and is presented in columns as the p-ERK1/2 expression relative to ERK expression. The experiment was repeated twice with similar results.</p

Regulation of FGFR1 mRNA expression in sh cells and MCF-7 cells.

<p>Expression of total FGFR1 or FGFR1IgIIIc was quantified by qRT-PCR in the cells cultured as follows: A) The cells grown in standard growth medium were treated with PD173074 for 24 h. B) The cells were grown without testosterone (Te) for 5 days and without serum for 48 h. C) The FGF-8b-overexpressing S115 cell lines (FGF8b1 and FGF8b14) and the transfection control cell lines (Mock1 and Mock3) were cultured in 4% DC-FBS in the absence of Te. D) shLacZ cells were grown without Te for 2 days and without serum for 24 h followed by treatment with FGF-8b (25 ng/ml) for 24 h. E) MCF-7 cells were grown in standard growth medium and treated similarly with FGF-8. The experiment was performed as triplicates and repeated twice with similar results. The statistical difference between the vehicle- and FGF-8b-treated cells was determined by independent sample t-test, * <i>P</i><0.05.</p