E2F1 activation is responsible for pituitary adenomas induced by HMGA2 gene overexpression

The High Mobility Group protein HMGA2 is a nuclear architectural factor that plays a critical role in a wide range of biological processes including regulation of gene expression, embryogenesis and neoplastic transformation. Several studies are trying to identify the mechanisms by which HMGA2 protein is involved in each of these activities, and only recently some new significant insights are emerging from the study of transgenic and knock-out mice. Overexpression of HMGA2 gene leads to the onset of prolactin and GH-hormone induced pituitary adenomas in mice, suggesting a critical role of this protein in pituitary tumorigenesis. This was also confirmed in the human pathology by the finding that HMGA2 amplification and/or overexpression is present in human prolactinomas. This review focuses on recent data that explain the mechanism by which HMGA2 induces the development of pituitary adenomas in mice. This mechanism entails the activation of the E2F1 protein by the HMGA2-mediated displacement of HDAC1 from pRB protein

HIPK2 in cancer biology and therapy: Recent findings and future perspectives

Homeodomain-interacting protein kinase 2 (HIPK2) is a serine-threonine kinase that phosphorylates and regulates a plethora of transcriptional regulators and chromatin modifiers. The heterogeneity of its interactome allows HIPK2 to modulate several cellular processes and signaling pathways, ultimately regulating cell fate and proliferation. Because of its p53-dependent pro-apoptotic activity and its downregulation in many tumor types, HIPK2 is traditionally considered a bone fide tumor suppressor gene. However, recent findings revealed that the role of HIPK2 in the pathogenesis of cancer is much more complex, ranging from tumor suppressive to oncogenic, strongly depending on the cellular context. Here, we review the very recent data emerged in the last years about the involvement of HIPK2 in cancer biology and therapy, highlighting the various alterations of this kinase (downregulation, upregulation, mutations and/or delocalization) in dependence on the cancer types. In addition, we discuss the recent advancement in the understanding the tumor suppressive and oncogenic functions of HIPK2, its role in establishing the response to cancer therapies, and its regulation by cancer-associated microRNAs. All these data strengthen the idea that HIPK2 is a key player in many types of cancer; therefore, it could represent an important prognostic marker, a factor to predict therapy response, and even a therapeutic target itself

Anti-VEGF Therapy in Breast and Lung Mouse Models of Cancers

Cancer is the second leading cause of death in the world after cardiovascular diseases. Some types of cancer cells often travel to other parts of the body through blood circulation or lymph vessels, where they begin to grow. This process is recognized as metastasis. Angiogenesis is the formation of new blood vessels from existing vessel. Normally angiogenesis is a healthy process, that helps the body to heal wounds and repair damaged body tissues, whereas in cancerous condition this process supports new blood vessels formation that provide a tumor with its own blood supply, nutrients and allow it to grow. The most important proximal factor for angiogenesis is the vascular endothelial growth factor VEGF. Angioinhibition is a form of targeted therapy that uses drugs to stop tumors from making new blood vessels. Therefore, in this paper we analyse the importance of VEGF as target of cancer therapy, analysing murine models

Nrf2 Pathway in Age-Related Neurological Disorders: Insights into MicroRNAs

A general hallmark of neurological diseases is the loss of redox homeostasis that triggers oxidative damages to biomolecules compromising neuronal function. Under physiological conditions the steady-state concentrations of reactive oxygen species (ROS) and reactive nitrogen species (RNS) are finely regulated for proper cellular functions. Reduced surveillance of endogenous antioxidant defenses and/or increased ROS/RNS production leads to oxidative stress with consequent alteration of physiological processes. Neuronal cells are particularly susceptible to ROS/RNS due to their biochemical composition. Overwhelming evidences indicate that nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-linked pathways are involved in protective mechanisms against oxidative stress by regulating antioxidant and phase II detoxifying genes. As such, Nrf2 deregulation has been linked to both aging and pathogenesis of many human chronic diseases, including neurodegenerative ones such as Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. Nrf2 activity is tightly regulated by a fine balance between positive and negative modulators. A better understanding of the regulatory mechanisms underlying Nrf2 activity could help to develop novel therapeutic interventions to prevent, slow down or possibly reverse various pathological states. To this end, microRNAs (miRs) are attractive candidates because they are linked to intracellular redox status being regulated and, post-transcriptionally, regulating key components of ROS/RNS pathways, including Nrf2

La Candelaria Ridge (NW Argentina) as a natural lab for the exploration of the geothermal system of Rosario de La Frontera: Methods and preliminary results

Within the scientific framework recently proposed by C.U.I.A. (Consorzio Universitario Italiano per l’Argentina) for the development of applied researches on the Argentina territory, several research groups, belonging to selected Italian and Argentina Universities, converged in the last year on the research line devoted to the “Sustainable development of future towns”. This contribution focuses on the preliminary results achieved by this collaboration among the Universities of Camerino, Jujuy, Roma Tre, Salta, Sapienza. The project focuses on the application of robust methodologies and the development of new ones to explore the geothermal potential of the area of Rosario de La Frontera (NW Argentina) located at the northern edge of La Candelaria Ridge, one of positively inverted structures cropping out between the provinces of Salta and Tucuman. It belongs to the Santa Barbara System of the Andes retro-wedge...Fil: Maffucci, R.. Università Roma Tre III; ItaliaFil: Caffe, Pablo Jorge. Universidad Nacional de Jujuy. Instituto de Geología Minera; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta; ArgentinaFil: Corrado, Sveva. Università Roma Tre III; ItaliaFil: Invernizzi, Ciro. Università degli Studi di Camerino; ItaliaFil: Giordano, G.. Università Roma Tre III; ItaliaFil: Pierantoni, Pablo. Università degli Studi di Camerino; ItaliaFil: Viramonte, Jose Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta; Argentina. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Instituto Geonorte; Argentin