Vasohibin‑2 promotes proliferation in human breast cancer cells via upregulation of fibroblast growth factor‑2 and growth/differentiation factor‑15 expression.
Vasohibin‑2 promotes proliferation in human breast cancer cells via upregulation of fibroblast growth factor‑2 and growth/differentiation factor‑15 expression.
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Vasohibin-2 通过上调成纤维细胞生长因子-2 和生长/分化因子-15 表达促进人乳腺癌细胞增殖
DOI：
10.3892/mmr.2014.2317
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发表时间：
2014-08
影响因子：
3.4
通讯作者：
Gao W
中科院分区：
文献类型：
--
作者：
Tu M;Liu X;Han B;Ge Q;Li Z;Lu Z;Wei J;Song G;Cai B;Lv N;Jiang K;Wang S;Miao Y;Gao W
血管hibin-2 （Vasohibin-2, VASH2）是一种血管生成因子，以前报道过是一种与癌症相关的基因，具有细胞质和核型形式。本研究采用免疫组织化学方法研究了VASH2在人乳腺癌组织及癌旁非癌组织中的表达。用慢病毒构建体转染MCF-7和BT474人乳腺癌细胞，建立体外VASH2过表达和敲低模型。此外，将转染的细胞皮下接种BALB/cA裸鼠，建立VASH2过表达和敲低的体内模型。采用体外溴脱氧尿苷法和异种移植瘤Ki67免疫组化研究VASH2对细胞增殖的影响。使用人生长因子阵列研究生长因子，并通过免疫印迹进一步确认某些因子。结果表明，细胞质VASH2在Ki67（增殖标志物）水平≥14%的乳腺癌组织中的表达水平高于Ki67水平<14%的组织。VASH2在体外和体内诱导增殖。VASH2激活的四种生长因子分别为：成纤维细胞生长因子2 （FGF2）、生长/分化因子15 （GDF15）、胰岛素样生长因子结合蛋白（IGFBP）3和IGFBP6。FGF2和GDF15可能有助于vash2诱导的增殖。目前的研究确定了VASH2在人类乳腺癌中的新作用，这一知识表明VASH2可能是乳腺癌治疗的新靶点。
Vasohibin-2 (VASH2) is an angiogenic factor, and has been previously reported to be a cancer-related gene, with cytoplasmic and karyotypic forms. In the current study VASH2 expression in human breast cancer tissue and adjacent non-cancerous tissue was investigated with immunohistochemistry. MCF-7 and BT474 human breast cancer cells were transfected with lentiviral constructs to generate in vitro VASH2 overexpression and knockdown models. In addition, BALB/cA nude mice were inoculated subcutaneously with transfected cells to generate in vivo models of VASH2 overexpression and knockdown. The effect of VASH2 on cell proliferation was investigated using a bromodeoxyuridine assay in vitro and immunohistochemistry of Ki67 in xenograft tumors. Growth factors were investigated using a human growth factor array, and certain factors were further confirmed by an immunoblot. The results indicated that the expression level of cytoplasmic VASH2 was higher in breast cancer tissues with a Ki67 (a proliferation marker) level of ≥14%, compared with tissues with a Ki67 level of <14%. VASH2 induced proliferation in vitro and in vivo. Four growth factors activated by VASH2 were identified as follows: Fibroblast growth factor 2 (FGF2), growth/differentiation factor-15 (GDF15), insulin-like growth factor-binding protein (IGFBP)3 and IGFBP6. FGF2 and GDF15 may contribute to VASH2-induced proliferation. The current study identified a novel role for VASH2 in human breast cancer, and this knowledge suggests that VASH2 may be a novel target in breast cancer treatment.
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影响因子：
8.8
作者：
Shoker, B S;Jarvis, C;Davies, M P;Iqbal, M;Sibson, D R;Sloane, J P
通讯作者：
Sloane, J P
影响因子：
11.5
作者：
Chitnis, Meenali M.;Yuen, John S. P.;Macaulay, Valentine M.
通讯作者：
Macaulay, Valentine M.
DOI：
10.1093/jnci/88.9.601
发表时间：
1996-05-01
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Rocha, RL;Hilsenbeck, SG;Yee, D
通讯作者：
Yee, D
影响因子：
8.5
作者：
Heidebrecht, HJ;Buck, F;Parwaresch, R
通讯作者：
Parwaresch, R
DOI：
10.1152/physiol.00045.2009
发表时间：
2010-04
期刊：
Physiology (Bethesda, Md.)
影响因子：
--
作者：
Witsch E;Sela M;Yarden Y
通讯作者：
Yarden Y