Heparin-binding secretory transforming gene (hst) facilitates rat lactotrope cell tumorigenesis and induces prolactin gene transcription.
Heparin-binding secretory transforming gene (hst) facilitates rat lactotrope cell tumorigenesis and induces prolactin gene transcription.
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肝素结合分泌转化基因（hst）促进大鼠催乳素细胞肿瘤发生并诱导催乳素基因转录。
DOI：
10.1172/jci118388
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Melmed,S
中科院分区：
文献类型：
--
作者：
Shimon,I;Huttner,A;Said,J;Spirina,OM;Melmed,S
我们以前已经表明，人泌乳素瘤表达肝素结合分泌转化基因（hst），编码成纤维细胞生长因子-4（FGF-4）的转化序列。为了阐明hst在垂体肿瘤发生中的作用，我们用重组FGF-4处理了原代大鼠垂体和垂体肿瘤细胞培养物，并用全长人hst cDNA稳定转染了垂体细胞系。筛选hst mRNA表达和FGF-4产生的转染子。FGF-4（0.1-50 ng/ml）可使GH4细胞催乳素（PRL）分泌量增加2.5倍（P < 0.001），原代培养中PRL分泌量增加60%（P < 0.05），但生长激素分泌量减少（P < 0.001）。GH4 hst转染细胞基础PRL分泌明显增加（3倍，P < 0.001），细胞增殖速度加快（P < 0.001）。FGF-4处理野生型GH4细胞，瞬时转染含有荧光素酶报告基因的表达构建体（rPRL.luc）驱动的rPRL启动子，导致剂量依赖性增加高达3.3倍的PRL转录活性。通过组织学侵袭性和增殖细胞核抗原染色评估，来自体内皮下注射强表达FGF-4的GH4 hst转染细胞的肿瘤生长更具侵袭性（P < 0.01）。结果表明，hst过表达介导催乳细胞肿瘤生长，并有力地刺激PRL合成。因此，hst可能通过其分泌蛋白FGF-4的旁分泌或自分泌作用直接促进泌乳素瘤的发展。
We have shown previously that human prolactinomas express transforming sequences of the heparin-binding secretory transforming gene (hst) which encodes fibroblast growth factor-4 (FGF-4). To elucidate the role of hst in pituitary tumorigenesis we treated primary rat pituitary and pituitary tumor cell cultures with recombinant FGF-4 and also stably transfected pituitary cell lines with full-length human hst cDNA. Transfectants were screened for hst mRNA expression and FGF-4 production. FGF-4 (0.1-50 ng/ml) caused a dose-dependent 2.5-fold increase of prolactin (PRL) secretion (P < 0.001) in GH4 cells and up to 60% (P < 0.05) in primary cultures, while decreasing growth hormone release (P < 0.001). GH4 hst transfectants displayed markedly enhanced basal PRL secretion (threefold, P < 0.001) and also proliferated faster (P < 0.001). FGF-4 treatment of wild-type GH4 cells, transiently transfected with an expression construct (rPRL.luc) containing a luciferase reporter driven by the rPRL promoter, resulted in a dose-dependent increase of up to 3.3-fold in PRL transcriptional activity. Tumors derived from in vivo subcutaneous injection of GH4 hst-transfected cells strongly expressing FGF-4 grew more aggressively as assessed by histologic invasiveness and proliferating cell nuclear antigen staining (P < 0.01). The results indicate that hst overexpression mediates lactotrope tumor growth and potently stimulates PRL synthesis. Thus, hst may directly facilitate prolactinoma development via paracrine or autocrine action of its secreted protein, FGF-4.
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小仓鼠肾细胞成纤维细胞生长因子受体的鉴定和部分表征。
DOI：
--
发表时间：
1985
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Neufeld,G;Gospodarowicz,D
通讯作者：
Gospodarowicz,D
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DOI：
--
发表时间：
1989
期刊：
Oncogene research
影响因子：
--
作者：
Velcich,A;Delli-Bovi,P;Mansukhani,A;Ziff,EB;Basilico,C
通讯作者：
Basilico,C
影响因子：
5.8
作者：
HERMAN, V;FAGIN, J;MELMED, S
通讯作者：
MELMED, S
影响因子：
15.9
作者：
ALEXANDER, JM;BILLER, BMK;KLIBANSKI, A
通讯作者：
KLIBANSKI, A
hst 癌基因的染色体定位及其与人类黑色素瘤中 int.2 癌基因的共扩增。
影响因子：
8
作者：
J. Adélaı̈de;M. Mattei;I. Marics;F. Raybaud;J. Planche;O. Delapeyrière;D. Birnbaum
通讯作者：
D. Birnbaum