Epidermal growth factor and hepatocyte growth factor receptors collaborate to induce multiple biological responses in bovine mammary epithelial cells

The aim of this work was to explore whether epidermal growth factor (EGF) and hepatocyte growth factor (HGF) could increase the biological responses of a mammary epithelial cell line of bovine origin when added simultaneously. We also investigated a possible molecular mechanism underlying this cooperation. The development of mammary gland requires several circulating and locally produced hormones. Hepatocyte growth factor and its tyrosine kinase receptor, mesenchymal-epithelial transition factor (MET), are expressed and temporally regulated during mammary development and differentiation. Epidermal growth factor receptor and its ligands have also been implicated in the growth and morphogenesis of the mammary epithelium. Both EGF and HGF seem to exert a morphogenic program in this tissue; therefore, we hypothesized that these cytokines could act cooperatively in bovine mammary epithelial cells. We have already shown that the bovine BME-UV cell line, a nontumorigenic mammary epithelial line, expresses both MET and EGF receptor. Simultaneous treatment with HGF and EGF elicited an increase in proliferation, dispersion, degradation of extracellular matrix, and motility. Following EGF treatment, BME-UV mammary cells exhibited an increase in MET expression at both the mRNA and protein levels. Long-term treatment of BME-UV cells with HGF and EGF together increased the level of activation of the extracellular signal-regulated kinase 1/2 and protein kinase B signaling pathways when compared with HGF or EGF alone. These data outline a possible cooperative role of the EGF and HGF pathways and indicate that cross-talk between their respective receptors may modulate mammary gland development in the cow

La valutazione sociale delle occupazioni nell’Italia contemporanea: una nuova scala per vecchie ipotesi

The paper presents the new version of the social desirability scale of occupations for Italy, a reputational scale whose first version was built by de Lillo and Schizzerotto (1985) following Goldthorpe and Hope (1974). First we discuss the main reasons that led the research team to undertake this task. Prestige scales are known indeed to be fairly stable across time and space; however Italian society has undergone profound changes over the last 20 years, and the stability of (the perception of) the occupational stratification needed to be proved.The research design is pretty similar to the one used in 1985; however the interviewees sample is much numerous (N = 1958) and the occupations graded amount to 686. Each occupation received around 60 evaluations; occupations have been grouped into 110 categories, which form the scale. We present the criteria which underlie the scale categories, and discuss the main features of the ranking resulting from giving them a score derived from respondents’ ratings.As a research tool, we provide the conversion rules between ISCO88 and our scale, showing that even when all the relevant information for translating the ISCO88 codes into the scores of our scale (sector of activity, self employment, etc.) is not available the conversion between the two classification tools is of a good quality.The main research hypotheses tested here is that the ratings – and so the scale – do not differ according to subgroup variations among respondents, i.e. that gender, age, education, place of residence and occupation do not influence in a systematic way respondents’ ratings. The hypothesis is confirmed, however with two exceptions. First, some occupations have been graded in a systematically different way in the different areas of the country (north west, north east, centre, south, islands), though place of residence in itself does not have an influence on the scale as a whole. Second, the highly educated rated better those occupations which require high education – though this effect is a minor one. More insight will be gained from future analyses

La valutazione sociale delle occupazioni nell’Italia contemporanea: una nuova scala per vecchie ipotesi

The paper presents the new version of the social desirability scale of occupations for Italy, a reputational scale whose first version was built by de Lillo and Schizzerotto (1985) following Goldthorpe and Hope (1974). First we discuss the main reasons that led the research team to undertake this task. Prestige scales are known indeed to be fairly stable across time and space; however Italian society has undergone profound changes over the last 20 years, and the stability of (the perception of) the occupational stratification needed to be proved.The research design is pretty similar to the one used in 1985; however the interviewees sample is much numerous (N = 1958) and the occupations graded amount to 686. Each occupation received around 60 evaluations; occupations have been grouped into 110 categories, which form the scale. We present the criteria which underlie the scale categories, and discuss the main features of the ranking resulting from giving them a score derived from respondents’ ratings.As a research tool, we provide the conversion rules between ISCO88 and our scale, showing that even when all the relevant information for translating the ISCO88 codes into the scores of our scale (sector of activity, self employment, etc.) is not available the conversion between the two classification tools is of a good quality.The main research hypotheses tested here is that the ratings – and so the scale – do not differ according to subgroup variations among respondents, i.e. that gender, age, education, place of residence and occupation do not influence in a systematic way respondents’ ratings. The hypothesis is confirmed, however with two exceptions. First, some occupations have been graded in a systematically different way in the different areas of the country (north west, north east, centre, south, islands), though place of residence in itself does not have an influence on the scale as a whole. Second, the highly educated rated better those occupations which require high education – though this effect is a minor one. More insight will be gained from future analyses

Effect of Echinacea augustifolia extract on cell viability and differentiation in mammary epithelial cells

Echinacea spp. are popularly used as an herbal medicine or food supplement for enhancing the immune system and activating biological property in different tissues. In this study we show the biological effect of Echinacea augustifolia extract on cell viability and cell differentiation in mammary epithelial cell lines. These effects have been observed in two different cell line derived from mouse (HC11) and bovine (BME-UV). Echinacea extract enhanced cell liability from 100 to 1000 ng/ml in association with growth factors, epidermal growth factor (EGF) or insulin, but also without EGF (p<0.05) up to 37% vs. control. This effect may be modulated by MAPK and Akt activation that Echinacea extract treatment increased and/or by a reduction of caspase 3 activity, showed a dose–response decrease after Echinacea treatment. Finally Echinacea extract was able to increase (p<0.05) at 100 ng/ml beta-casein expression in association with PRL (5 ug/ml). These data demonstrate that Echinacea angustifolia extract can stimulate mammary epithelial cell physiology and may be considered a candidate to support mammary gland activity during a mammogenetic and lactogenetic state

Curcuminoid phospholipid complex induces apoptosis in mammary epithelial cells by STAT-3 signaling

Curcumin (from the rhizome of Curcuma longa) is well documented for its medicinal properties in Indian and Chinese systems of medicine where it is widely used for the treatment of several diseases. Epidemiological observations are suggestive that curcumin consumption may reduce the risk of some form of cancers and provide other protective biological effects in humans. These biological properties have been attributed to curcuminoids that have been widely studied for their anti-inflammatory, anti-angiogenic, antioxidant, wound healing and anti-cancer effects. In this study we have investigated on the effect of a curcumin phospholipid complex on mammary epithelial cell viability. HC11 and BME-UV cell lines, validated models to study biology of normal, not tumoral, mammary epithelial cells, were used to analyse these effects. We report that curcumin acts on STAT-3 signal pathway to reduce cell viability and increase apoptosis evaluated by the the amount of activated caspase 3. Further it reduces MAPK and AKT activations. JSI-124, a STAT-3 inhibitor (100 nM) was able to block the negative effect of curcumin on cell viability and caspase 3 activation. Finally the negative effect of cucumin on cell viability has been impaired in STAT-3i HC11, where STAT-3 protein was greatly reduced by shRNA-interference. These results indicate that curcumin presents a potential adverse effect to normal mammary epithelial cells and that it has a specific effect on signal trasduction in mammary epithelium

Epidermal growth factor and hepatocyte growth factor cooperate to enhance cell proliferation, scatter, and invasion in murine mammary epithelial cells

The development of the mammary gland requires an integrated response to specific growth factors and steroid hormones. Hepatocyte growth factor (HGF) and its tyrosine kinase receptor, MET, are expressed and temporally regulated during mammary development and differentiation. Epidermal growth factor receptor (EGFR) and its ligands have also been implicated in mammary gland growth and morphogenesis. Since both cytokines seem to exert a morphogenic program in this tissue, we have investigated the possible concerted action of EGF and HGF on the HC11 cell line, a widely used model of nontumorigenic mammary cells. Western blot analysis indicated that HC11 expressed MET and EGFR, and showed ERK1/2 and AKT activation following HGF or EGF treatment. Analysis by real-time PCR and western blot showed that after an EGF but not HGF or insulin-like growth factor-I treatment, HC11 mammary cells exhibited an increase in MET expression at both the mRNA and protein levels, which was dependent on the AKT pathway. Simultaneous treatment with HGF and EGF increased proliferation, scatter, and invasion as assessed by cell count, cell cycle, scatter, and transwell assays. AKT inhibition did not influence the cooperation on proliferation or invasion after HGF+EGF treatment, while ERK1/2 inhibition abolished MET/EGFR cooperation on proliferation. HGF+EGF treatment increased the duration of ERK1/2 and AKT activation compared to HGF or EGF alone. All these data indicate that a crosstalk between the EGF and HGF pathways in mammary epithelial cells may modulate the development of the mammary gland

Positive effect of silymarin on cell growth and differentiation in bovine and murine mammary cells

Silymarin, a naturally acknowledged hepatoprotector used in humans to treat liver diseases has been tested in murine (HC11) and bovine (BME-UV) mammary epithelial cell lines to evaluate a possible direct effect on cell growth and differentiation in mammary gland. Silymarin enhanced cell proliferation (p < 0.05) from 10 to 1000 ng/ml in association with growth factors, (up to 20%) or alone (up to 15%) versus controls. Furthermore, silymarin (100 ng/ml) was able to increase (p < 0.05) beta-casein gene expression alone or in association with prolactin (5 microg/ml). These effects may be related with protein kinase B (AKT) activation induced by silymarin treatment (p < 0.05) and/or by a dose-related inhibitory effect (p < 0.05) on caspase-3 activity related to a protective role in cell apoptosis. These data suggest that silymarin should be considered a candidate to support mammary gland activity during a lactogenetic state