Open AccessChicken ovalbumin upstream promoter transcription factor II in human breast carcinoma: Possible regulator of lymphangiogenesis via vascular endothelial growth factor‐C expression
Author(s) -
Nagasaki Shuji,
Suzuki Takashi,
Miki Yasuhiro,
Akahira Junichi,
Shibata Hirotaka,
Ishida Takanori,
Ohuchi Noriaki,
Sasano Hironobu
Publication year - 2009
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2008.01078.x
Subject(s) - breast cancer , estrogen receptor , breast carcinoma , lymphangiogenesis , cancer research , biology , gene knockdown , medicine , vascular endothelial growth factor , cancer , metastasis , cell culture , genetics , vegf receptors
Chicken ovalbumin upstream promoter transcription factors (COUP‐TF) are orphan members of the nuclear receptor superfamily and consist of COUP‐TFI and COUP‐TFII. COUP‐TFI was reported to be overexpressed in human breast cancer and to promote estrogen‐independent transcriptional activity of estrogen receptor α. COUP‐TFII, however, has not been examined in the breast. Therefore, we carried out immunohistochemical analysis of COUP‐TFII in human breast cancer in order to clarify its biological and clinical significance. We immunolocalized COUP‐TFII in 119 human breast cancers and correlated the findings with various clinicopathological parameters. Fifty‐nine percent of the cases were immunohistochemically positive for COUP‐TFII. COUP‐TFII positivity was correlated with poor clinical outcome, and a statistically significant correlation was detected between COUP‐TFII and the following clinicopathological parameters: clinical stage, lymph node status, histological grade, and estrogen receptor α status. In addition, short interfering RNA‐mediated knockdown of COUP‐TFII in the breast carcinoma cell line MCF‐7 decreased the level of vascular endothelial growth factor‐C mRNA expression, which is a known inducer of lymphangiogenesis and lymph node metastasis. These results suggest that COUP‐TFII is involved in the development of advanced human breast cancer. ( Cancer Sci 2009; 100: 639–645)