TRANSFECTED INSULIN-LIKE GROWTH FACTOR-II MODULATES THE MITOGENIC RESPONSE OF RAT THYROCYTES IN CULTURE

TRANSFECTED INSULIN-LIKE GROWTH FACTOR-II MODULATES THE MITOGENIC RESPONSE OF RAT THYROCYTES IN CULTURE
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DOI:
10.1016/0303-7207(92)90170-b
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发表时间:
1992-07-01
影响因子:
4.1
通讯作者:
TRAMONTANO, D
TRAMONTANO, D
中科院分区:
医学2区
文献类型:
--
作者:
VENEZIANI, BM;DIMARINO, C;TRAMONTANO, D

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用编码大鼠胰岛素样生长因子Ⅱ(IGF-II)的序列转染的大鼠甲状腺细胞(FRTL 5)在大多数获得的克隆(Tr克隆)中呈现对转染的IGF-II特异的mRNA。Tr 7和Tr 12细胞对促甲状腺激素(TSH)的促有丝分裂作用保持反应能力,而外源性IGF-I、IGF-II或胰岛素均不能刺激其增殖。在不存在外源有丝分裂原的情况下,Tr 7和Tr 12克隆将[H-3]胸苷强力掺入DNA中。该活性被针对大鼠IGF-II的单克隆抗体sm1.2显著抑制。Tr 7和Tr 12克隆具有I型IGF受体,已知其介导IGF-II的促有丝分裂作用,其亲和力与亲本细胞膜上存在的亲和力相似,但能力降低。最后,培养基条件Tr 7和Tr 12增加基础胸苷掺入静止FRTRL 5细胞和扩增,诱导TSH。内源性IGFs可能通过调节TSH的促有丝分裂作用和支持TSH非依赖性生长,在甲状腺细胞增殖的调节中发挥重要作用。
Rat thyroid cells (FRTL5), transfected with thc sequence coding for rat insulin-like growth factor II (IGF-II) presented mRNA specific for the transfected IGF-II in most of the clones obtained (Tr clones). Tr7 and Tr12 cells maintained their ability to respond to thc mitogenic effect of thyrotropin (TSH), while either exogenous IGF-I or IGF-II or insulin failed to stimulate their proliferation. In the absence of exogenous mitogens the Tr7 and Tr12 clones vigorously incorporated [H-3]thymidine into DNA. This activity was significantly inhibited by sm1.2, a monoclonal antibody against rat IGF-II. Tr7 and Tr12 clones possess type I IGF receptors, known to mediate the mitogenic effect of IGF-II, with affinity similar to those present on the membrane of the parental cells but with reduced capacity. Finally, media conditioned by Tr7 and Tr12 increase basal thymidine incorporation in quiescent FRTRL5 cells and amplify that induced by TSH. Endogenous IGFs may play an important role in the regulation of thyroid cell proliferation by modulating the mitogenic effect of TSH and by supporting TSH-independent growth.