Focal amplification and oncogene dependency of GAB2 in breast cancer

Bocanegra, M,Bergamaschi, A,Kim, Y H,Miller, M A,Rajput, A B,Kao, J,Langerød, A,Han, W,Noh, D -Y,Jeffrey, S S,Huntsman, D G,Børresen-Dale, A -L,Pollack, J R Macmillan Publishers Limited 2010 Oncogene Vol.29 No.5

DNA amplifications in breast cancer are frequent on chromosome 11q, in which multiple driver oncogenes likely reside in addition to cyclin D1 (CCND1). One such candidate, the scaffolding adapter protein, GRB2-associated binding protein 2 (GAB2), functions in ErbB signaling and was recently shown to enhance mammary epithelial cell proliferation, and metastasis of ERBB2 (HER2/neu)-driven murine breast cancer. However, the amplification status and function of GAB2 in the context of amplification remain undefined. In this study, by genomic profiling of 172 breast tumors, and fluorescence in situ hybridization validation in an independent set of 210 scorable cases, we observed focal amplification spanning GAB2 (11q14.1) independent of CCND1 (11q13.2) amplification, consistent with a driver role. Further, small interfering RNA (siRNA)-mediated knockdown of GAB2 in breast cancer lines (SUM52, SUM44PE and MDA468) with GAB2 amplification revealed a dependency on GAB2 for cell proliferation, cell-cycle progression, survival and invasion, likely mediated through altered phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signaling. GAB2 knockdown also reduced proliferation and survival in a cell line (BT474) with ERBB2 amplification, consistent with the possibility that GAB2 can function downstream of ERBB2. Our studies implicate focal amplification of GAB2 in breast carcinogenesis, and underscore an oncogenic role of scaffolding adapter proteins, and a potential new point of therapeutic intervention.

Characteristics and Nutritional and Cardiovascular-Health Properties of Seaweeds

Bocanegra, Aranzazu,Bastida, Sara,Benedi, Juana,Rodenas, Sofia,Sanchez-Muniz, Francisco J. The Korean Society of Food Science and Nutrition 2009 Journal of medicinal food Vol.12 No.2

While marine algae have traditionally formed part of the Oriental diet, their major use in Western countries has been in the phytocolloid industry. Only a few coastal communities outside Asia have customarily used seaweeds as components of special dishes. Of late, however, seaweeds have gained importance as foodstuffs in Western countries and most recently as components of functional foods because of their high dietary fiber, mineral, vitamin, and phytochemical content, low energy levels, and high concentrations of certain polyunsaturated fatty acids. The present paper reviews the available data for some of the components of the major edible algae and studies several factors that can affect their physiochemical properties (e.g., hydration, water and oil-holding capacity, fermentability, binding capacity, etc.) and, in turn, their nutritional importance. The effects of marine alga consumption on growth and body weight, mineral availability, lipid metabolism, blood pressure, and antioxidant properties are reviewed, together with preliminary data on the effects of some functional foods containing seaweeds on lipid metabolism and gene expression of enzymes engaged in antioxidant protection. This review concludes with some remarks regarding the danger of the improper use of seaweeds in herbal medications. In addition, as the properties of algae are highly dependent on their individual composition, any generalization regarding these properties may be considered misleading and scientifically inappropriate.

Characteristics and Nutritional and Cardiovascular-Health Properties of Seaweeds

Aránzazu Bocanegra,Sara Bastida,Juana Benedí,Sofía Ródenas,Francisco J. Sánchez-Muniz 한국식품영양과학회 2009 Journal of medicinal food Vol.12 No.2

While marine algae have traditionally formed part of the Oriental diet, their major use in Western countries has been in the phytocolloid industry. Only a few coastal communities outside Asia have customarily used seaweeds as components of special dishes. Of late, however, seaweeds have gained importance as foodstuffs in Western countries and most recently as components of functional foods because of their high dietary fiber, mineral, vitamin, and phytochemical content, low energy levels, and high concentrations of certain polyunsaturated fatty acids. The present paper reviews the available data for some of the components of the major edible algae and studies several factors that can affect their physiochemical properties (e.g., hydration, water and oil-holding capacity, fermentability, binding capacity, etc.) and, in turn, their nutritional importance. The effects of marine alga consumption on growth and body weight, mineral availability, lipid metabolism, blood pressure, and antioxidant properties are reviewed, together with preliminary data on the effects of some functional foods containing seaweeds on lipid metabolism and gene expression of enzymes engaged in antioxidant protection. This review concludes with some remarks regarding the danger of the improper use of seaweeds in herbal medications. In addition, as the properties of algae are highly dependent on their individual composition, any generalization regarding these properties may be considered misleading and scientifically inappropriate.

<i>CAMK1D</i> amplification implicated in epithelial–mesenchymal transition in basal-like breast cancer

Bergamaschi, Anna,Kim, Young H.,Kwei, Kevin A.,La Choi, Yoon,Bocanegra, Melanie,Langerød, Anita,Han, Wonshik,Noh, Dong-Young,Huntsman, David G.,Jeffrey, Stefanie S.,Børresen-Dale, Anne-Lise,Pollack, J Elsevier 2008 Molecular Oncology Vol.2 No.4

<P><B>Abstract</B></P><P>Breast cancer exhibits clinical and molecular heterogeneity, where expression profiling studies have identified five major molecular subtypes. The basal-like subtype, expressing basal epithelial markers and negative for estrogen receptor (ER), progesterone receptor (PR) and HER2, is associated with higher overall levels of DNA copy number alteration (CNA), specific CNAs (like gain on chromosome 10p), and poor prognosis. Discovering the molecular genetic basis of tumor subtypes may provide new opportunities for therapy. To identify the driver oncogene on 10p associated with basal-like tumors, we analyzed genomic profiles of 172 breast carcinomas. The smallest shared region of gain spanned just seven genes at 10p13, including calcium/calmodulin-dependent protein kinase ID (<I>CAMK1D</I>), functioning in intracellular signaling but not previously linked to cancer. By microarray, <I>CAMK1D</I> was overexpressed when amplified, and by immunohistochemistry exhibited elevated expression in invasive carcinomas compared to carcinoma <I>in situ</I>. Engineered overexpression of CAMK1D in non-tumorigenic breast epithelial cells led to increased cell proliferation, and molecular and phenotypic alterations indicative of epithelial–mesenchymal transition (EMT), including loss of cell–cell adhesions and increased cell migration and invasion. Our findings identify <I>CAMK1D</I> as a novel amplified oncogene linked to EMT in breast cancer, and as a potential therapeutic target with particular relevance to clinically unfavorable basal-like tumors.</P>

Physical Properties of the Sr4Al6O12SO4 Ceramic Compound

J.A. Rodríguez-García,E. Rocha-Rangel,J. López Hernández,C.A. Hernández Bocanegra,A.L. Leal Cruz,J.M. Almanza Robles,J. Torres Torres 한양대학교 세라믹연구소 2017 Journal of Ceramic Processing Research Vol.18 No.11

The Sr4Al6O12SO4 ceramic compound was synthesized by a solid state reaction starting from stoichiometric mixtures of 3 : 3 : 1 molar ratio of reactive grade of SrCO3, Al2O3 and SrSO4, respectively. Cylindrical samples were confirmed by uniaxial pressing at 100 MPa and were heat treated at 1400 oC during 4 hrs. Subsequently, the samples were ground and re-conformed in cylindrical shape samples by uniaxial pressing at 300 MPa. The new samples were heat treated at 1400 oC during 24 hrs. This process was done in order to increase density of the samples. The Sr4Al6O12SO4 ceramic compound was characterized by the study of its physical properties such as: density, micro-hardness, thermal expansion and stability, enthalpy of formation, magnetic properties and electrical conductivity. Experimental results show that the maximum density obtained for the Sr4Al6O12SO4 ceramic compound was 2.913 grcm−3, with thermal expansion coefficient of 10.12E−06(oC−1); it also presents an enthalpy of 2.3 KJmol-1 and an excellent thermal stability at elevated temperatures in different atmospheres. In addition, the Sr4Al6O12SO4 ceramic compound is neither electrically conductive nor magnetic.