Identification of PRG1, a novel progestin-responsive gene with sequence homology to 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase
Identification of PRG1, a novel progestin-responsive gene with sequence homology to 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase
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DOI：
10.1210/me.11.4.490
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发表时间：
1997-04-01
影响因子：
--
通讯作者：
Watts, CKW
中科院分区：
文献类型：
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作者：
Hamilton, JA;Callaghan, MJ;Watts, CKW
为了确定β-内酰胺酶蛋白作用的早期分子靶点，使用差异显示技术鉴定用合成β-内酰胺酶蛋白ORG 2058处理3小时的T-47 D乳腺癌细胞中表达水平改变的基因。PRG 1首先被分离为200 bp的cDNA克隆，其孕激素调节作用通过北方分析得到证实。PRG 1的完整编码区的克隆显示，它与来自几种组织和物种的酶6-磷酸果糖-2-激酶/果糖-2，6-二磷酸酶的亚型具有高度的氨基酸序列同一性。PRG 1 mRNA的表达在几种正常乳腺上皮细胞和乳腺癌细胞系以及各种人体组织中观察到，在乳腺、主动脉和脑中表达最高。在T-47 D细胞中，PRG 1 mRNA被孕激素快速瞬时诱导，表达在2 - 4 h之间达到峰值，并在12 h时恢复至对照水平。孕激素诱导的PRG 1 mRNA的增加受到抑制的催乳素拮抗剂RU 486，并通过孕激素受体发生。孕激素诱导PRG 1 mRNA也被放线菌素D抑制，但不被放线菌酮。因此，PRG 1是一种新的人类基因，通过孕激素受体直接受孕激素调控。
To define early molecular targets of progestin action, the differential display technique was used to identify genes with altered levels of expression in T-47D breast cancer cells treated with the synthetic progestin ORG 2058 for 3 h. PRG1 was first isolated as a 200-bp cDNA clone and its progestin regulation confirmed by Northern analysis. Cloning of the complete coding region of PRG1 revealed that it shared a high degree of amino acid sequence identity with isoforms of the enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase from several tissues and species. Expression of PRG1 mRNA was observed in several normal breast epithelial and breast cancer cell lines and in a variety of human tissues, with highest expression in the breast, aorta, and brain. In T-47D cells, PRG1 mRNA was rapidly and transiently induced by progestins, expression peaking between 2 and 4 h and returning to control levels by 12 h. Progestin-induced increases in PRG1 mRNA were inhibited by the progestin antagonist RU 486 and occurred via the progesterone receptor. Progestin induction of PRG1 mRNA was also inhibited by actinomycin D but not by cycloheximide. PRG1 is therefore a novel human gene that is directly regulated by progestins via the progesterone receptor.