15-Hydroxyprostaglandin dehydrogenase associates with poor prognosis in breast cancer, induces epithelial-mesenchymal transition, and promotes cell migration in cultured breast cancer cells.
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15-Hydroxyprostaglandin dehydrogenase associates with poor prognosis in breast cancer, induces epithelial-mesenchymal transition, and promotes cell migration in cultured breast cancer cells. / Lehtinen, Laura; Vainio, Paula; Wikman, Harriet; Reemts, Johannes; Hilvo, Mika; Issa, Rana; Pollari, Sirkku; Brandt, Burkhard; Oresic, Matej; Pantel, Klaus; Kallioniemi, Olli; Iljin, Kristiina.
In: J PATHOL, Vol. 226, No. 4, 4, 2012, p. 674-686.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - 15-Hydroxyprostaglandin dehydrogenase associates with poor prognosis in breast cancer, induces epithelial-mesenchymal transition, and promotes cell migration in cultured breast cancer cells.
AU - Lehtinen, Laura
AU - Vainio, Paula
AU - Wikman, Harriet
AU - Reemts, Johannes
AU - Hilvo, Mika
AU - Issa, Rana
AU - Pollari, Sirkku
AU - Brandt, Burkhard
AU - Oresic, Matej
AU - Pantel, Klaus
AU - Kallioniemi, Olli
AU - Iljin, Kristiina
PY - 2012
Y1 - 2012
N2 - 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-? 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.
AB - 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-? 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.
KW - Humans
KW - Female
KW - Prognosis
KW - Survival Rate
KW - Cell Line, Tumor
KW - Gene Expression Regulation, Neoplastic
KW - Tissue Array Analysis
KW - Gene Silencing
KW - Cell Adhesion
KW - Germany/epidemiology
KW - Wound Healing
KW - Adenocarcinoma/enzymology/genetics/mortality/secondary
KW - Arachidonic Acid/metabolism
KW - Breast Neoplasms/enzymology/genetics/mortality/pathology
KW - Cell Movement/genetics
KW - Cell Survival/genetics
KW - Epithelial-Mesenchymal Transition
KW - Hydroxyprostaglandin Dehydrogenases/genetics/metabolism
KW - Lymph Nodes/metabolism/pathology
KW - Humans
KW - Female
KW - Prognosis
KW - Survival Rate
KW - Cell Line, Tumor
KW - Gene Expression Regulation, Neoplastic
KW - Tissue Array Analysis
KW - Gene Silencing
KW - Cell Adhesion
KW - Germany/epidemiology
KW - Wound Healing
KW - Adenocarcinoma/enzymology/genetics/mortality/secondary
KW - Arachidonic Acid/metabolism
KW - Breast Neoplasms/enzymology/genetics/mortality/pathology
KW - Cell Movement/genetics
KW - Cell Survival/genetics
KW - Epithelial-Mesenchymal Transition
KW - Hydroxyprostaglandin Dehydrogenases/genetics/metabolism
KW - Lymph Nodes/metabolism/pathology
M3 - SCORING: Journal article
VL - 226
SP - 674
EP - 686
JO - J PATHOL
JF - J PATHOL
SN - 0022-3417
IS - 4
M1 - 4
ER -
