TY - JOUR
T1 - Ikaros is expressed in human extravillous trophoblasts and involved in their migration and invasion
AU - Yamamoto, E.
AU - Ito, T.
AU - Abe, A.
AU - Sido, F.
AU - Ino, K.
AU - Itakura, A.
AU - Mizutani, S.
AU - Dovat, S.
AU - Nomura, S.
AU - Kikkawa, F.
N1 - Funding Information:
We thank the laboratory of Dr Charles H. Graham (Queen’s University, Ontario, Canada) for generous gift of HTR-8/SVneo cells and Dr Tomohiro Yagi (Kyoto Prefectural University of Medicine, Kyoto, Japan) for providing the construct HA-Ik6. This research was partly supported by grants-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, from the Ministry of Public management, Home affairs, Posts and Telecommunications of Japan for specific medical research (in collaboration with Nagoya Teishin Hospital) and from the Ogya fund.
PY - 2005/11
Y1 - 2005/11
N2 - The transcriptional factor Ikaros was originally found to function as a key regulator of lymphocyte differentiation. In addition, we have reported that Ikaros regulates the human placental leucine aminopeptidase (P-LAP)/insulin-regulated aminopeptidase (IRAP) gene in choriocarcinoma trophoblastic cells, suggesting that Ikaros might be involved in placental development, while even its presence in human placenta remains undetermined. We therefore sought to clarify the location and roles of Ikaros in human placenta. Immunohistochemical analysis showed modest Ikaris expression in syncytium, and intense expression in extravillous trophoblasts (EVTs) in first trimester placenta. Western blot analysis showed that villous trophoblasts principally expressed Ikaros-2/3, while Ikaros-x (Ikx) was predominantly expressed in cultured EVTs. Furthermore, to investigate the functional role of Ikx in EVTs, the EVT cell line HTR-8/SVneo was infected with a retrovirus vector expressing the hemagglutinin (HA)-tagged dominant negative isoform Ikaros-6 (Ik6), which prevents the DNA-binding activity of Ikx. Antibody against HA showed successful transduction of Ik6 in HTR-8/SVneo cells on immunocytochemistry and Western blotting. Transduction of Ik6 significantly reduced the migratory and invasive abilities of HTR-8/SVneo cells. These results suggest that Ikx is involved in migration and invasion of EVTs in early placentation.
AB - The transcriptional factor Ikaros was originally found to function as a key regulator of lymphocyte differentiation. In addition, we have reported that Ikaros regulates the human placental leucine aminopeptidase (P-LAP)/insulin-regulated aminopeptidase (IRAP) gene in choriocarcinoma trophoblastic cells, suggesting that Ikaros might be involved in placental development, while even its presence in human placenta remains undetermined. We therefore sought to clarify the location and roles of Ikaros in human placenta. Immunohistochemical analysis showed modest Ikaris expression in syncytium, and intense expression in extravillous trophoblasts (EVTs) in first trimester placenta. Western blot analysis showed that villous trophoblasts principally expressed Ikaros-2/3, while Ikaros-x (Ikx) was predominantly expressed in cultured EVTs. Furthermore, to investigate the functional role of Ikx in EVTs, the EVT cell line HTR-8/SVneo was infected with a retrovirus vector expressing the hemagglutinin (HA)-tagged dominant negative isoform Ikaros-6 (Ik6), which prevents the DNA-binding activity of Ikx. Antibody against HA showed successful transduction of Ik6 in HTR-8/SVneo cells on immunocytochemistry and Western blotting. Transduction of Ik6 significantly reduced the migratory and invasive abilities of HTR-8/SVneo cells. These results suggest that Ikx is involved in migration and invasion of EVTs in early placentation.
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U2 - 10.1093/molehr/gah239
DO - 10.1093/molehr/gah239
M3 - Article
C2 - 16364975
AN - SCOPUS:32144461153
SN - 1360-9947
VL - 11
SP - 825
EP - 831
JO - Molecular Human Reproduction
JF - Molecular Human Reproduction
IS - 11
ER -