title: Cyclin D1 Co-localizes with Beclin-1 in Glioblastoma Recurrences: A Clue to a Therapy-induced, Autophagy-mediated Degradative Mechanism?
abstract: BACKGROUND
  Glioblastoma (GB) recurrences are rarely removed, therefore, tissue modifications induced by radiotherapy, and temozolomide chemotherapy are scarcely known. Nuclear cyclin D1 is associated with GB progression and resistance to therapy. We previously found that the expression of autophagic protein beclin-1 is a major determinant of prognosis in GB.
  
  
  METHODS
  In 31 patients with primary GB and their recurrences, we investigated the protein expression of cyclin D1 and beclin-1, before and after radiotherapy-temozolomide therapy by immunohistochemistry.
  
  
  RESULTS
  Most (20/31) primary GBs were negative for nuclear cyclin D1, and highly expressed beclin-1. In their recurrences, cytoplasmic cyclin D1 positivity was observable, which co-localized with beclin-1. Eleven primary GBs instead exhibited low beclin-1 expression and were positive for nuclear cyclin D1; three of their recurrences exhibited an increase of beclin-1, which co-localized with cyclin D1 in the cytoplasm.
  
  
  CONCLUSIONS
  Our results suggest therapy-induced degradation of cyclin D1 via autophagy.
authors.affiliation: Tuscan Tumor Institute, Florence, Italy Unit of Radiation Oncology, Department of Medicine, Surgery, and Neurosciences, University and Hospital of Siena, Siena, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Pirtoli
authors.affiliation: Tuscan Tumor Institute, Florence, Italy Unit of Radiation Oncology, Department of Medicine, Surgery, and Neurosciences, University and Hospital of Siena, Siena, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Belmonte
authors.affiliation: Tuscan Tumor Institute, Florence, Italy Unit of Radiation Oncology, Department of Medicine, Surgery, and Neurosciences, University and Hospital of Siena, Siena, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Toscano
authors.affiliation: Tuscan Tumor Institute, Florence, Italy Unit of Radiation Oncology, Department of Medicine, Surgery, and Neurosciences, University and Hospital of Siena, Siena, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Tini
authors.affiliation: Tuscan Tumor Institute, Florence, Italy Unit of Pathological Anatomy, Department of Medicine, Surgery, and Neurosciences, University and Hospital of Siena, Siena, Italy miracco@unisi.it.
authors.forename: Clelia
authors.initials: C
authors.lastname: Miracco
mesh_terms: D000328:Adult; D017209:Apoptosis; D001343:Autophagy / Q000235:genetics; D000071186:Beclin-1 / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000096:biosynthesis* / Q000235:genetics; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D011379:Prognosis; D000077204:Temozolomide
chemical_list: D000071186:Beclin-1; C530104:CCND1 protein, human; D019938:Cyclin D1; D003606:Dacarbazine; D000077204:Temozolomide
keywords: Glioblastoma recurrences; beclin-1; cyclin D1 degradation; radiation and temozolomide therapy