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 p53(high) and p53(low) 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.