title: Calponin h1 suppresses tumor growth of Src-induced transformed 3Y1 cells in association with a decrease in angiogenesis.
abstract: Calponin h1 (CNh1) is a basic actin-binding protein that is abundantly expressed in smooth muscle cells and involved in smooth muscle contraction by inhibiting actomyosin MgATPase. In recent studies, CNh1 was noted to suppress cell proliferation and tumorigenicity in leiomyosarcoma and tumor growth in fibrosarcoma cell lines. To further investigate the function of CNh1 as a tumor suppressor, we transfected the human CNh1 gene into a v-src-transformed rat fibroblast cell line SR-3Y1. The volume of the tumors derived from one randomly selected CNh1-transfectant (C1) in nude mice was reduced to 34.1% of that from a randomly selected vector transfectant (V1). A similar tendency was observed in another independent pair (C2, V2). Pathological analysis showed a significant decrease in the number of mitotic cells in the CNh1-transfectants. Further, a marked reduction in the number of vessels in the CNh1-transfectant was observed. DNA synthesis under conditions without serum was significantly reduced in the CNh1-transfectant (C1) compared with the control transfectant (V1), while no significant difference was seen in the cellular growth in the presence of 10% serum. A slight but significant reduction in in vitro cellular motility in the CNh1-transfectant was also observed. While the suppression of growth potential and cell motility by CNh1 transfer was significant but partial, a marked reduction in vascular endothelial growth factor (VEGF) mRNA and the secretion of VEGF protein was observed in the CNh1-transfectant. These results suggest that CNh1 plays a role as tumor suppressor in SR-3Y1 mainly by decreasing VEGF expression and angiogenesis in vivo and partially through reducing cellular proliferative potential and cell motility.
authors.affiliation: Department of Dermatology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
authors.forename: Miwako
authors.initials: M
authors.lastname: Kaneko
authors.forename: Michiko
authors.initials: M
authors.lastname: Takeoka
authors.forename: Misae
authors.initials: M
authors.lastname: Oguchi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Koganehira
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Murata
authors.forename: Takashi
authors.initials: T
authors.lastname: Ehara
authors.forename: Minoru
authors.initials: M
authors.lastname: Tozuka
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Saida
authors.forename: Shun'ichiro
authors.initials: S
authors.lastname: Taniguchi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D002455:Cell Division; D002461:Cell Line, Transformed; D002465:Cell Movement; D016228:Endothelial Growth Factors / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008840:Microfilament Proteins; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000096985:Calponins
chemical_list: D002135:Calcium-Binding Proteins; D002148:Calmodulin-Binding Proteins; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D008840:Microfilament Proteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000096985:Calponins