Browsing by Author "Panno, Maria Luisa"

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    Estrogen receptor alpha interferes with LKBl/AMPK/mTOR signaling activation in adiponectin-treated breast cancer cells
    (2018-02-27) Naimo, Giuseppina Daniela; Andò, Sebastiano; Panno, Maria Luisa; Mauro, Loredana
    Breast cancer is the most common type of tumor and the leading cause of cancer-related deaths in women, worldwide. The cause of breast cancer is multifactorial and includes hormonal, genetic and environmental cues. Obesity is now an accepted risk factor for breast cancer in postmenopausal women, particularly for the hormone-dependent subtype of mammary tumor. Obesity has regarded as a multifactorial disorder characterized by an increased number and size of adipocytes. Adipose tissue is an active metabolic and endocrine organ that secretes many adipocytokines, which act as key mediators in several obesity-associated diseases. Among these, adiponectin represents the most abundant adipose tissue-excreted protein, which exhibits insulin sensitizing, antiinflammatory, and antiatherogenic properties Adiponectin has been proposed as having a key role in the pathogenesis of cardiovascular disease and type 2 diabetes along with obesity-associated malignancies, such as breast cancer. An inverse correlation is reported between obesity and adiponectin, for which low levels of adiponectin represent a risk factor for breast cancer. The role of adiponectin on breast tumorigenesis seems to be dependent on cell phenotypes. Indeed, several in vitro and in vivo studies demonstrated that low adiponectin levels repressed growth in ER-negative breast cancer cells whereas increased proliferation in ER- positive cells. Adiponectin interacts with specific receptors and exerts its effects, including regulation of cell survival, apoptosis and metastasis, via a plethora of signaling pathways. The key molecule of adiponectin action is AMP-activated protein kinase (AMPK), which is mainly activated by liver kinase B1 (LKB1). On the basis of this observations, the aim of the present study was to investigate the effect of adiponectin on LKB1/AMPK signaling in ER-negative (MDA-MB-231) and positive (MCF-7) breast cancer cells. In MCF-7 cells, upon low adiponectin levels, ER impaired LKB1/AMPK interaction by recruiting LKB1 as coactivator at nuclear level, sustaining breast tumor growth. In this condition, AMPK signaling was not working, letting fatty acid synthesis still active. In contrast, in MDA-MB-231 cells the phosphorylated status of AMPK and ACC appeared enhanced, with consequent inhibition of both lipogenesis and cell growth. Thus, in the presence of adiponectin, ERα signaling switched energy balance of breast cancer cells towards a lipogenic phenotype. The same results on tumor growth were reproduced in a xenograft model. These results emphasize how adiponectin action in obese patients is tightly dependent on ERα, addressing that adiponectin may work as growth factor in ERα- positive breast cancer cells.
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    L'assunzione del genotipo neuroendocrino da parte di cellule epiteliali neoplastiche quale fattore di resistenza all'aggressione terapeutica nell'ademacarcinoma prostatico
    (2014-11-25) Ferraro, Aurora; Canonaco, Marcello; Cerra, Maria Carmela; omeo, Francesco; Panno, Maria Luisa
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    L'uso di biomateriali innovativi per la veicolazione di farmaci antitumorali
    (2014-12-01) Tavolaro, Palmira; Sisci, Diego; Andò, Sebastiano; Panno, Maria Luisa; Tavolaro, Adalgisa
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    Pathway infiammatorio del Sistema del Complemento nelle ascidie: sequenziamento e caratterizzazione funzionale del recettore dell’anafilatossina C3a di Ciona intestinalis
    (2014-03-26) Melillo, Daniela; Tota, Bruno; Panno, Maria Luisa; Pinto, Maria Rosaria
    In mammals, the bioactive fragment C3a, released from C3 during complement activation, is a potent mediator of inflammatory reactions and exerts its functional activity through the specific binding to cell surface G protein-coupled seven-transmembrane receptors. Recently, a C3a-mediated chemotaxis of hemocytes has been demonstrated in the deuterostome invertebrate Ciona intestinalis and an important role for this molecule in inflammatory processes has been suggested. In this study, we have cloned and characterized the CiC3aR molecule involved in the CiC3a-mediated chemotaxis and studied its expression profile. The sequence of CiC3aR, encoding a 95,394 Da seventransmembrane domain protein, shows the highest sequence homology with mammalian C3aRs. Northern blot analysis revealed that the CiC3aR is expressed abundantly in the heart and neural complex and to a lesser extent, in the ovaries, hemocytes, and larvae. Three polyclonal antibodies raised against peptides corresponding to CiC3aR regions of the first and second extracellular loop and of the third intracellular loop, react specifically in Western blotting with a single band of 98-102 kDa in hemocyte protein extracts. Immunostaining performed on circulating hemocytes with the three specific antibodies revealed that CiC3aR is constitutively expressed only in hyaline and granular amoebocytes. In chemotaxis experiments, the antibodies against the first and second extracellular loop inhibited directional migration of hemocytes toward the synthetic peptide reproducing the CiC3a C-terminal sequence, thus providing the compelling evidence that C. intestinalis.expresses a functional C3aR homologous to the mammalian receptor. These findings further elucidate the evolutionary origin of the vertebrate complement-mediated proinflammatory process