Cyclin D1 Co-localizes with Beclin-1 in Glioblastoma Recurrences: A Clue to a Therapy-induced, Autophagy-mediated Degradative Mechanism?

Anticancer Res. 2016 Aug;36(8):4057-62.

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.

Patients and 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.

Conclusion: Our results suggest therapy-induced degradation of cyclin D1 via autophagy.

Keywords: Glioblastoma recurrences; beclin-1; cyclin D1 degradation; radiation and temozolomide therapy.

MeSH terms

  • Adult
  • Apoptosis
  • Autophagy / genetics
  • Beclin-1 / biosynthesis*
  • Beclin-1 / genetics
  • Cell Line, Tumor
  • Cyclin D1 / biosynthesis*
  • Cyclin D1 / genetics
  • Dacarbazine / administration & dosage
  • Dacarbazine / analogs & derivatives
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Glioblastoma / drug therapy
  • Glioblastoma / genetics*
  • Glioblastoma / pathology
  • Glioblastoma / radiotherapy
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / radiotherapy
  • Prognosis
  • Temozolomide

Substances

  • Beclin-1
  • CCND1 protein, human
  • Cyclin D1
  • Dacarbazine
  • Temozolomide