title: Overexpression of endogenous TIMP-2 increases the proliferation of BeWo choriocarcinoma cells through the MAPK-signaling pathway.
abstract: Choriocarcinoma is a highly malignant form of trophoblastic tumor that is characterized by malignant placental tumors and rapid cell growth. In vivo and in vitro studies have demonstrated that tissue inhibitor of metalloproteinase 2 (TIMP-2) is present in choriocarcinoma. However, the role of TIMP-2 in cell proliferation in choriocarcinoma has not been investigated. Exogenous TIMP-2 is known to promote cell proliferation. During growth, cells are subjected to varied concentrations of TIMP-2, which depend on the amount of TIMP-2 produced by the cells themselves. Thus, the effect of gradually increasing endogenous TIMP-2 on the proliferation of choriocarcinoma cells needs to be examined. Proliferation of BeWo human choriocarcinoma cells was stimulated by transient transfection of a plasmid expressing TIMP-2. Overexpression of endogenous TIMP-2 also activated ERK1/2 and JNK1/2 of the MAPK-signaling pathway. Furthermore, inhibition of these proteins resulted in suppression of the cell proliferation-stimulating effect of TIMP-2. These results suggest that TIMP-2 plays an important role in tumor growth in the case of BeWo cells. Moreover, proliferation of BeWo cells due to TIMP-2 expression can be used as a model for fast-growing choriocarcinomas, and TIMP-2 could be used as a novel tumor marker of choriocarcinoma.
authors: 1Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors: Nguyen Manh
authors: NM
authors: Thang
authors: Keiichi
authors: K
authors: Kumasawa
authors: Tateki
authors: T
authors: Tsutsui
authors: Hitomi
authors: H
authors: Nakamura
authors: Hidetake
authors: H
authors: Masaki
authors: Tomoko
authors: T
authors: Ono
authors: Tadashi
authors: T
authors: Kimura
mesh_terms: D049109:Cell Proliferation; D002822:Choriocarcinoma / Q000201:enzymology* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis*
chemical_list: C560823:TIMP2 protein, human; D019716:Tissue Inhibitor of Metalloproteinase-2
keywords: BeWo cell; MAPK pathway; cell proliferation; tissue inhibitors of metalloproteinase 2