Breast cancer is the most frequent
cancer and the leading cause of
cancer-related deaths in women worldwide. The prognosis of
breast cancer is tightly correlated with the degree of spread beyond the primary tumour.
Arachidonic acid (AA) and
prostaglandin E(2) (
PGE(2)) are known to regulate tumour
metastasis enabling epithelial-mesenchymal transition (EMT). However, the detailed role of
15-hydroxyprostaglandin dehydrogenase (HPGD), the key
enzyme degrading
prostaglandin E(2) , remains unclear in
breast cancer. Here, we show that HPGD
mRNA is overexpressed in a subset of clinical breast
cancers compared to normal breast tissue samples and that high HPGD
mRNA expression associates with poor prognosis. Immunohistochemical staining of primary
breast cancer and
lymph node metastasis tissue samples confirmed high HPGD
protein expression in 20% of the samples, as well as associated HPGD expression with aggressive characteristics, such as increased risk of disease relapse and shorter disease-free survival. Results from cultured cells indicated abundant HPGD expression in highly metastatic
breast cancer cells, and impairment of HPGD expression using RNA interference led to a significant decrease in
transforming growth factor-β signalling, in cellular
arachidonic acid levels as well as in cell migration. Furthermore, gene expression microarray analysis followed by quantitative RT-PCR validation showed that HPGD silencing decreased
aryl hydrocarbon receptor signalling and induced mesenchymal-epithelial transition. In conclusion, our results indicate that HPGD is highly expressed in metastatic and aggressive
breast cancer and promotes EMT and migration in
breast cancer cells.