Prostate Cancer Biology

carbone_group

Members

Alyssa Paganoni, MS Student
Azzurra Mutti, MS Student
Dheeraj Shinde, PhD
Domenico Albino, PhD
Giuseppina Carbone, MD (head)
Marita Zoma, PhD student

Overview

Research in our group is focused on the study of the molecular mechanisms that control prostate cancer development and progression. Cancer of the prostate is the most common cancer and one of leading causes of cancer related death. At the present there is a need to understand the mechanisms involved in the pathogenesis of this disease and find the means to distinguish between cancers that may need different therapeutic strategies. One of our goals is to identify and characterize the transcription factor cascade that control prostate cancer development. Cell growth and differentiation processes are regulated at the level of gene transcription. Many transcription factors possess transforming potential when expressed in a deregulated fashion. ETS factors constitute a network of transcriptional regulators that activate or repress the expression of genes that are involved in various biological processes, including cellular proliferation, apoptosis, invasiveness and cancer progression. The laboratory has identified ETS genes potentially involved in prostate cancer, based upon their altered expression in prostate cancer clinical samples. Currently, the functional role of these genes is being investigated as well as their relevance for diagnosis, prognosis and therapy. We are also investigating novel therapeutic approaches to target oncogenic ETS factors.

 

Main projects

  • The ETS transcription factor ESE3/EHF as a regulator of prostate epithelial cell differentiation and stem cell properties.
  • Functional, clinical and therapeutic impact of epigenetic cross-talks in ERG fusion positive prostate cancers.
  • MicroRNA network regulated by ETS transcription factors in prostate cancer

 

Current Fundings

  • Swiss National Science Foundation (SNSF) PI,Giuseppina Carbone
  • Oncosuisse/Swiss Cancer League PI, Giuseppina Carbone

Comprehensive Publication list

 

  1. Dallavalle C, Albino D, Civenni G, Merulla J, Ostano P, Mello-Grand M, Rossi S, Losa M, D’Ambrosio G, Sessa F, Thalmann GN, Garcia-Escudero R, Zitella A, Chiorino G, Catapano CV, Carbone GM. J Clin Invest. 2016 Nov 7. pii: 86505. doi: 10.1172/JCI86505.
  2. Albino D, Civenni G, Rossi S, Catapano CV, Carbone GM. The ETS factor ESE3/EHF represses IL-6 and restrains prostate cancer stem–like compartment. Oncotarget. 2016 Oct 8. doi: 10.18632/oncotarget.12525.
  3. Albino D, Civenni G, Dallavalle C, Roos M, Jahns H, Curti L, Rossi S, Pinton S, D’Ambrosio G, Sessa F, Hall J, Catapano CV, Carbone GM. Activation of the Lin28/let-7 Axis by Loss of ESE3/EHF Promotes a Tumorigenic and Stem-like Phenotype in Prostate Cancer. Cancer Res. 2016 Jun 15;76(12):3629-43. doi: 10.1158/0008-5472.CAN-15-2665. Epub 2016 May 2. PubMed PMID: 27197175.
  4. Gianluca Civenni, Nicole Longoni, Paula Costales, Cecilia Dallavalle, Cristina García Inclán, Domenico Albino, Luz Elena Nuñez, Francisco Morís2, Giuseppina M. Carbone and Carlo V. Catapano. EC-70124, a novel glycosylated indolocarbazole multi-kinase inhibitor, reverts tumorigenic and stem cell properties in prostate cancer by inhibiting STAT3 and NF-κB. Molecular Cancer Ther,15,5 2016.
  5. Brambilla L, Genini D, Laurini E, Merulla J, Perez L, Fermeglia M, Carbone GM, Pricl S, Catapano CV. Hitting the right spot: Mechanism of action of OPB-31121, a novel and potent inhibitor of the Signal Transducer and Activator of Transcription 3 (STAT3). Mol Oncol. 2015 Mar 5. pii: S1574-7891(15)00048-4. doi: 10.1016/j.molonc.2015.02.012.
  6. Madhuri Kalathur, Alberto Toso, Jingjing Chen, Ajinkya Revandkar, Claudia Danzer-Baltzer, Ilaria Guccini, Abdullah Alajati, Manuela Sarti, Sandra Pinton, Lara Brambilla, Diletta Dimitri, Giuseppina Carbone, Ramon Garcia-Escudero, Alessandro Padova, Letizia Magnoni, Alessia Tarditi, Laura Maccari, Federico Malusa, Ravi Kiran Kalathur, Lorenzo Pinna, Maria Ruzzene, Giorgio Cozza, Carlo Catapano, Ian Frew, Nicolas Delaleu and Andrea Alimonti. A chemogenomic and shRNA screenings identify CK2 as a novel target for pro-senescence therapy in PTEN deficient tumors. Nature Communication, 2015.
  7. Sarti M, Pinton S, Limoni C, Carbone GM, Pagani O, Cavalli F, Catapano CV.Differential expression of testin and survivin in breast cancer subtypes. Oncol Rep. 2013 Aug;30(2):824-32.
  8. Longoni N, Sarti M, Albino D, Civenni G, Malek A, Ortelli E, Pinton S, Mello-Grand M, Ostano P, D’Ambrosio G, Sessa F, Garcia-Escudero R, Thalmann GN, Chiorino G, Catapano CV, Carbone GM. The ETS Transcription Factor ESE1/ELF3 Orchestrates a Positive Feedback Loop That Constitutively Activates NF-κB and Drives Prostate Cancer Progression. Cancer Res. 2013 Jul 15;73 (14):4533-47.
  9. Civenni G., Malek A., Albino D., Garcia-Escudero R., Napoli S., Di Marco S., Pinton S., Sarti M., Carbone G.M, Catapano, C.V. RNAi-mediated silencing of Myc transcription inhibits stem-like cell maintenance and tumorigenicity in prostate cancer. Cancer Res. 2013; 73(22): 6816-27.
  10. Albino D, Longoni N, Curti L, Mello-Grand M, Pinton S, Civenni G, Thalmann G, D’Ambrosio G, Sarti M, Sessa F, Chiorino G, Catapano CV, Carbone GM. ESE3/EHF controls epithelial cell differentiation and its loss leads to prostate tumors with mesenchymal and stem-like features. Cancer Res. 2012 Jun 1;72(11):2889-900.
  11. Longoni N, Kunderfranco P, Pellini S, Albino D, Mello-Grand M, Pinton S, D’Ambrosio G, Sarti M, Sessa F, Chiorino G, Catapano CV, Carbone GM. Aberrant expression of the neuronal-specific protein DCDC2 promotes malignant phenotypes and is associated with prostate cancer progression. Oncogene. 2012 Jun 25. doi: 10.1038/onc.2012.245.
  12. Malek A, Núñez LE, Magistri M, Brambilla L, Jovic S, Carbone GM, Morís F, Catapano CV. Modulation of the activity of Sp transcription factors by mithramycin analogues as a new strategy for treatment of metastatic prostate cancer. PLoS One. 2012;7(4):e35130.
  13. Babbio F, Pistore C, Curti L, Castiglioni I, Kunderfranco P, Brino L, Oudet P, Seiler R, Thalman GN, Roggero E, Sarti M, Pinton S, Mello-Grand M, Chiorino G, Catapano CV, Carbone GM, Bonapace IM. The SRA protein UHRF1 promotes epigenetic crosstalks and is involved in prostate cancer progression. Oncogene. 2012 Nov 15;31(46):4878-87.
  14. Carmen Jerónimo, Patrick J. Bastian, Anders Bjartell, Giuseppina M. Carbone, James W.F. Catto, Susan J. Clark, Rui Henrique, Francesco Montorsi, William G.Nelson, Shahrokh F. Shariat. (2011) Epigenetics in Prostate Cancer: biological and clinical relevance. European Urology Oct;60(4):753-66.
  15. Genini D, Garcia-Escudero R, Carbone GM, Catapano CV. Transcriptional and Non-Transcriptional Functions of PPARβ/δ in Non-Small Cell Lung Cancer. PLoSOne. 2012;7(9):e46009.
  16. Kunderfranco, P., Mello-Grand, M., Cangemi, R., Pellini, S., Mensah, A., Albertini, V., Malek, A., Chiorino, G., Catapano, C.V. and Carbone, G.M. ETS transcription factors control transcription of EZH2 and epigenetic silencing of the tumor suppressor gene Nkx3.1 in prostate cancer. PLoS One 5, e10547 (2010).
  17. Pastori, C., Magistri, M., Napoli, S., Carbone, G.M. & Catapano, C.V. Small RNA-directed transcriptional control: New insights into mechanisms and therapeutic applications. Cell Cycle 9, 2353-2362 (2010).
  18. Previdi, S., Malek, A., Albertini, V., Riva, C., Capella, C., Broggini, M., Carbone, G.M., Rohr, J. & Catapano, C.V. Inhibition of Sp1-dependent transcription and antitumor activity of the new aureolic acid analogues mithramycin SDK and SK in human ovarian cancer xenografts. Gynecol Oncol 118, 182-188 (2010)
  19. Jain A, Magistri M, Napoli S, Carbone GM and Catapano C.V. Mechanisms of Triplex DNA-mediated Inhibition of Transcription Initiation in Cells. Biochemie 2010.
  20. Napoli S, Pastori C, Magistri M, Carbone GM, Cavalli F. and Catapano C.V. Promoter-specific transcriptional interference and c-myc gene silencing by siRNAs in human cells. EMBO J. 2009 Jun 17;28(12):1708-19. Epub 2009 May 21.
  21. Genini D, Carbone GM and Catapano C.V. (2008) Multiple Interactions between Peroxisome Proliferators-Activated Receptors and the Ubiquitin-Proteasome System and Implications for Cancer Pathogenesis. PPAR Res, 2008, 195065.
  22. Romina Cangemi, Afua Mensah, Veronica Albertini, Maurizia Mello-Grand, Giovanna Chiorino, Carlo V. Catapano and Giuseppina M. Carbone.   Reduced expression and tumor suppressor function of the ETS transcription factor ESE-3 in prostate cancer. Oncogene 27, 2877-2885,2007.
  23. Sara Vignati, Veronica Albertini, Andrea Rinaldi, Ivo Kwee, Cristina Riva, Rita Oldrini, Carlo Capella, Francesco Bertoni, Giuseppina M. Carbone and Carlo V. Catapano. Cellular and molecular consequences of peroxisome proliferator-activated receptor-gamma activation in ovarian cancer cells. Neoplasia. Oct;8 (10):851-61 (2007)
  24. Veronica Albertini, Aklank Jain, Sara Vignati, Sara Napoli, Andrea Rinaldi, Ivo Kwee, Mohammad Nur-e-Alam, Julia Bergant, Francesco Bertoni, Giuseppina M. Carbone, Jurgen Rohr and Carlo V. Catapano. Novel GC-rich DNA binding compound produced by a genetically engineered mutant of the mithramyicin producer S.Argillaceus exhibits improved transcriptional repressor activity: implications for cancer therapy. Nucleic Acid. Res. 34(6): 1721-34, (2006).
  25. Napoli S, Negri U, Arcamone F, Capobianco ML, Carbone GMR, Catapano CV. Growth inhibition and apoptosis induced by daunomycin-conjugated triplex-forming oligonucleotides targeting the c-myc gene in prostate cancer cells. Nucleic Acids Res. 34(2):734-44 (2006).
  26. Carbone GMR, Napoli S, Valentini A, Cavalli F, Watson DK, Catapano CV. Triplex DNA-mediated downregulation of Ets2 expression results in growth inhibition and apoptosis in human prostate cancer cells. Nucleic Acid Res.32(14):4358-67(2005)
  27. Sara Napoli, Carbone GMR, Carlo Catapano, Nick Shaw, and Dev. P. Arya. Neomycin improves cationic lipid-mediated transfection of DNA in human cells.   Bioorg Med Chem Lett. 2005 Jul 15;15 (14):3467-9.
  28. Carbone GMR, Collier A, McGuffie EM, Catapano CV. Selective inhibition of transcription of the Est2 gene in prostate cancer cells by a triplex-forming oligonucleotide. Nucleic Acids Res. 31: 833-843 (2003).
  29. Remsing LL, Bahadori HR, Carbone GMR, McGuffie EM, Catapano CV, Rohr J. Inhibition of c-src transcription by mithramycin: structure-activity relationships of biosynthetically produced mithramycin analogues using the c-src promoter as target. Biochemistry 42: 8313-8324 (2003).
  30. Carbone GMR, McGuffie EM,NapoliS,Flanagan CE,Dembech C,Negri U,Arcamone F,Capobianco ML,and Catapano CV. DNA binding and antigene activity of a daunomycin-conjugated triplex-forming oligonucleotide targeting the P2 promoter of the human c-myc gene.Nucleic.Acid Res. 32(8):2396-410 (2004).
  31. Carbone GMR, Napoli S, Valentini A, Cavalli F, Watson DK, Catapano CV. Triplex DNA-mediated downregulation of Ets2 expression results in growth inhibition and apoptosis in human prostate cancer cells. Nucleic Acid Res.32(14):4358-67(2004)
  32. Carbone GMR, Catapano CV, Fernandes DJ: Imbalanced DNA synthesis induced by cytosine arabinoside and fludarabine in human leukemia cells. Biochem. Pharmacol., 62 (2001) 101-110.
  33. Catapano CV, Pacheco D, McGuffie EM, Carbone GMR: Inhibition of gene expression and cell proliferation by triple helix-forming oligonucleotides directed to the c-myc gene. Biochemistry 39:5126-5138 (2000).
  34. McGuffie EM, Pacheco D, Carbone GMR, Catapano CV: Antigene and antiproliferative effects of a c-myc-targeting phosphorothioate triple helix-forming oligonucleotides in human leukemia cells. Cancer Res 60:3790-3799 (2000).
  35. Catapano CV, Carbone GMR, Pisani F, Fernandes DJ: Arrest of replication fork progression at sites of VM-26-stabilized topoisomerase II-DNA complex formation in human CEM leukemia cells. Biochemistry 36:5739-5748 (1997).
  36. Catapano CV, Carbone GMR, Fernandes DJ: The nuclear matrix as a target for cancer therapy. Annals of Oncol 7:659-666 (1996).
  37. Carbone GMR, Sheikh AU, Zehnder T, Rose JC: Effect of chronic infusion of cortisol on renin gene expression and renin response to hemorrhage in fetal lambs at 0.65 gestation. Pediatr Res 37:316-20 (1995).
  38. Carbone GMR, St. Clair DK, Xu YA, Rose JC: Expression of manganese superoxide dismutase in ovine kidney cortex during development. Pediatr Res 35:41-4 (1994).
  39. Carbone GMR, Sheik AU, Rogers S, Brewer G, Rose JC: Developmental changes in renin gene expression in ovine kidney cortex. Am J Physiol 264:R591-596 (1993).