FUNCTION OF THE HOMEODOMAIN PROTEIN GHF1 IN PITUITARY CELL-PROLIFERATION
FUNCTION OF THE HOMEODOMAIN PROTEIN GHF1 IN PITUITARY CELL-PROLIFERATION
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DOI：
10.1126/science.1677216
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发表时间：
1991-07-12
期刊：
影响因子：
56.9
通讯作者：
KARIN, M
中科院分区：
文献类型：
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作者：
CASTRILLO, JL;THEILL, LE;KARIN, M
导致小鼠垂体侏儒症的突变存在于编码转录因子生长激素因子 1（GHF1 或pit1）的基因中。这些侏儒小鼠（dw 和 dw(J)）缺乏生长激素 (GH) 和催乳素 (PRL) 合成，并表现出垂体发育不全，表明存在干细胞缺陷。利用反义寡核苷酸技术，开发了这种遗传缺陷的细胞培养模型。互补寡核苷酸对 GHF1 合成的特异性抑制导致 GH 和 PRL 表达显着降低，并导致生长细胞系增殖显着降低。这些结果提供了直接证据，表明同源结构域蛋白 GHF1 不仅是分化表型的建立和维持所必需的，而且也是细胞增殖所必需的。
Mutations that cause pituitary dwarfism in the mouse reside in the gene encoding the transcription factor growth hormone factor 1 (GHF1 or pit1). These dwarf mice (dw and dw(J)) are deficient in growth hormone (GH) and prolactin (PRL) synthesis and exhibit pituitary hypoplasia, suggesting a stem cell defect. With antisense oligonucleotide technology, a cell culture model of this genetic defect was developed. Specific inhibition of GHF1 synthesis by complementary oligonucleotides led to a marked decrease in GH and PRL expression and to a marked decrease in proliferation of somatotrophic cell lines. These results provide direct evidence that the homeodomain protein GHF1 is required not only for the establishment and maintenance of the differentiated phenotype but for cell proliferation as well.