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BMC Cancer
Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

Breast cancers with high DSS1 expression that potentially maintains BRCA2 stability have poor prognosis in the relapse-free survival

Authors: Andri Rezano, Kazuhiko Kuwahara, Mutsuko Yamamoto-Ibusuki, Masahiro Kitabatake, Penpak Moolthiya, Suchada Phimsen, Taiji Suda, Shigenobu Tone, Yutaka Yamamoto, Hirotaka Iwase, Nobuo Sakaguchi

Published in: BMC Cancer | Issue 1/2013

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Abstract

Background

Genetic BRCA2 insufficiency is associated with breast cancer development; however, in sporadic breast cancer cases, high BRCA2 expression is paradoxically correlated with poor prognosis. Because DSS1, a mammalian component of the transcription/RNA export complex, is known to stabilize BRCA2, we investigated how the expression of DSS1 is associated with clinical parameters in breast cancers.

Methods

DSS1 mRNA and p53 protein were examined by RT-PCR and immunohistochemical staining of breast cancer specimens to classify DSS1 high and DSS1 low or p53high and p53low groups. Patient survival was compared using Kaplan-Meier method. DSS1 high or DSS1 low breast cancer cells were prepared by retroviral cDNA transfection or DSS1 siRNA on proliferation, cell cycle progression, and survival by flow cytometric analyses with or without anti-cancer drugs.

Results

In comparison to patients with low levels of DSS1, high-DSS1 patients showed a poorer prognosis, with respect to relapse-free survival period. The effect of DSS1 was examined in breast cancer cells in vitro. DSS1 high-expression reduces the susceptibility of MCF7 cells to DNA-damaging drugs, as observed in cell cycle and apoptosis analyses. DSS1 knockdown, however, increased the susceptibility to the DNA-damaging drugs camptothecin and etoposide and caused early apoptosis in p53 wild type MCF7 and p53-insufficient MDA-MB-231 cells. DSS1 knockdown suppresses the proliferation of drug-resistant MDA-MB-231 breast cancer cells, particularly effectively in combination with DNA-damaging agents.

Conclusion

Breast cancers with high DSS1 expression have worse prognosis and shorter relapse-free survival times. DSS1 is necessary to rescue cells from DNA damage, but high DSS1 expression increases drug resistance. We suggest that DSS1 expression could be a useful marker for drug resistance in breast cancers, and DSS1 knockdown can induce tumor apoptosis when used in combination with DNA-damaging drugs.
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Metadata
Title
Breast cancers with high DSS1 expression that potentially maintains BRCA2 stability have poor prognosis in the relapse-free survival
Authors
Andri Rezano
Kazuhiko Kuwahara
Mutsuko Yamamoto-Ibusuki
Masahiro Kitabatake
Penpak Moolthiya
Suchada Phimsen
Taiji Suda
Shigenobu Tone
Yutaka Yamamoto
Hirotaka Iwase
Nobuo Sakaguchi
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-562

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