BAG-4/SODD and associated antiapoptotic proteins are linked to aggressiveness of epithelial ovarian cancer

Clin Cancer Res. 2007 Nov 15;13(22 Pt 1):6585-92. doi: 10.1158/1078-0432.CCR-07-0327.

Abstract

Purpose: We hypothesized that elevated expression in ovarian cancer of the BAG family of prosurvival proteins and associated partners would be associated with clinical features of aggressiveness in ovarian cancer.

Experimental design: Expression patterns of BAG-1, BAG-3, BAG-4, and Bcl-xL were determined by immunohistochemical analysis of tissue samples obtained at diagnosis from 28 women with stage III or stage IV ovarian cancer treated with cisplatin, paclitaxel, and cyclophosphamide after initial cytoreduction. Association of these proteins, BAG-6, heat shock protein 70 (Hsp70), Hsp27, and Bcl-2, with clinical variables was tested in ovarian cancer tissue arrays from Gynecologic Oncology Group tissue bank.

Results: A statistically significant relationship was found between elevated cytoplasmic expression of BAG-4 and improved overall (P = 0.0002) and progression-free survival (P = 0.003) in the prospectively collected samples. Bcl-2 staining was significantly more frequent on the tissue array in lower stage (P = 0.005) and grade (P = 0.0009) tumors, whereas Hsp70 was prominent in higher grade cases (P = 0.002). Furthermore, Bcl-xL was more closely associated with serous compared with endometrioid ovarian cancers (P = 0.004).

Conclusion: Unexpectedly, cytoplasmic expression of BAG-4 and Bcl-2 marked less aggressive ovarian cancer, whereas nuclear Hsp70 suggested more aggressive behavior. Bcl-xL may play a more prominent function in the pathology of serous histology ovarian cancers compared with the endometrioid subtype. The findings presented here support involvement of these proteins in the propagation of ovarian cancer and provide a basis for the development of molecular therapeutics modulating these survival pathways.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adaptor Proteins, Signal Transducing / analysis
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis
  • Apoptosis Regulatory Proteins / analysis
  • Apoptosis Regulatory Proteins / metabolism*
  • Carcinoma / chemistry
  • Carcinoma / metabolism
  • Carcinoma / pathology*
  • Cell Nucleus / chemistry
  • Cell Nucleus / metabolism
  • Cytoplasm / chemistry
  • Cytoplasm / metabolism
  • Female
  • HSP70 Heat-Shock Proteins / analysis
  • HSP70 Heat-Shock Proteins / metabolism
  • Humans
  • Middle Aged
  • Ovarian Neoplasms / chemistry
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • bcl-X Protein / analysis
  • bcl-X Protein / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • BAG4 protein, human
  • HSP70 Heat-Shock Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-X Protein