43P - The high DSS1 expression involved in BRCA2 stability is a marker for breast cancer of poor prognosis

Date 08 May 2014
Event IMPAKT 2014
Session Welcome reception and Poster Walk
Topics Biomarkers
Breast Cancer
Presenter Andri Rezano
Citation Annals of Oncology (2014) 25 (suppl_1): i8-i16. 10.1093/annonc/mdu066
Authors A. Rezano1, K. Kuwahara2, M. Yamamoto-Ibusuki3, M. Kitabatake2, P. Moolthiya2, T. Suda4, S. Tone4, Y. Yamamoto3, H. Iwase3, N. Sakaguchi2
  • 1Cell Biology, Faculty of Medicine Padjadjaran University, 45363 - Jatinangor-West Java/ID
  • 2Immunology, Kumamoto University, 860-8556 - Kumamoto/JP
  • 3Breast And Endocrine Surgery, Kumamoto University, 860-8556 - Kumamoto/JP
  • 4Biochemistry And Electron Microscope Center, Kawasaki Medical School, 7010192 - Kurashiki/JP

Abstract

Background and Purpose:

Human DSS1 (deleted in split-hand/split-foot malformation) has been shown to interact with and stabilize the tumor suppressor protein BRCA2, which functions in homologous recombination repair of DNA damage. BRCA2 expression significantly correlated with histopathology grade III and was attributed with polymorphic nuclei and mitotic index suggesting that BRCA2 contributes to the proliferation rate in breast tumors; however, little is known concerning DSS1 expression in sporadic breast cancers.

Methods:

Gene expression studies revealed that high BRCA2 expression correlates with poor prognosis in clinical cases. We investigated the outcome of high DSS1 expression in clinical breast cancer cases. To clarify the role of DSS1 in breast cancer cells, we analyzed the effect of DSS1 on cells by DSS1 overexpression and depletion. The analyses include cell proliferation, cell cycle profile, DNA damage and drug susceptibility in both transfected cells.

Results:

The outcome of high DSS1 expression in clinical breast cancer significantly correlated with the shorter relapse-free survival times. DSS1 overexpression did not change the cellular proliferation but suppressed the cell death induced by DNA-damaging agents. Conversely, decrease of DSS1 expression in breast cancer cells caused apoptotic changes and enhanced drug sensitivity.

Conclusions:

DSS1 protein serves as a novel potential biomarker for diagnosis and treatment response of human breast cancer. Suppression of DSS1 expression in combination with chemotherapy might be effective for treatment of breast cancer of poor prognosis.

Disclosure:

All authors have declared no conflicts of interest.