Progestin increases gene transcription and messenger ribonucleic acid stability of fatty acid synthetase in breast cancer cells.
Progestin increases gene transcription and messenger ribonucleic acid stability of fatty acid synthetase in breast cancer cells.
复制标题
孕激素增加乳腺癌细胞中脂肪酸合成酶的基因转录和信使核糖核酸稳定性。
作者：
C. Joyeux;H. Rochefort;D. Chalbos
脂肪酸合成酶（FAS） mRNA 3′端cDNA克隆（Pg8）是目前在细胞系中研究内源基因受孕激素调控机制的为数不多的探针之一。已知合成黄体酮R5020可提高人乳腺癌细胞系MCF7中FAS mRNA的稳态水平。我们发现，在另一种黄体酮受体阳性细胞系T47D中也增加，但在黄体酮受体阴性细胞系BT20、MDA-MB231和HBL100中没有增加。在r5020处理的MCF7细胞中，FAS mRNA浓度随细胞密度的增加而升高。蛋白质合成抑制剂不能消除黄体酮诱导的FAS，提示黄体酮的主要作用。体外核运行转录实验表明，黄体酮可使FAS基因转录率提高约4倍。这种转录刺激在加入R5020后30分钟可检测到，并在4小时后达到最大，但不能完全解释mRNA稳态水平的总增加。在放线菌素D或虫草素存在下的Chase实验表明，黄体酮也将FAS mRNA的半衰期从6-9 h延长至24-33 h。我们得出结论，黄体酮通过增加基因的转录率和稳定mRNA来刺激FAS浓度。
The cDNA clone (Pg8) corresponding to the 3'-end of fatty acid synthetase (FAS) mRNA is one of the few probes to study in cell lines the mechanism by which an endogenous gene is regulated by progestins. The steady-state level of FAS mRNA is known to be increased by the synthetic progestin R5020 in the human breast cancer cell line MCF7. We show here that it is also increased in another progesterone-receptor-positive cell line T47D but not in progesterone-receptor-negative cell lines BT20, MDA-MB231, and HBL100. In R5020-treated MCF7 cells, the FAS mRNA concentration increased with cell density. Protein synthesis inhibitors did not abolish progestin induction of FAS suggesting a primary effect of the hormone. In vitro nuclear run-on transcription assays showed that the FAS gene transcription rate was increased about 4-fold by progestin. This stimulation of transcription was detectable 30 min after addition of R5020 and was maximal after 4 h, but could not totally account for the total increase in the mRNA steady state level. Chase experiments in the presence of Actinomycin D or Cordycepin showed that progestin also increased the half-life of FAS mRNA from 6-9 h to 24-33 h. We conclude that progestin stimulates the FAS concentration both by increasing the transcription rate of the gene and by stabilizing the mRNA.
孕激素对抗雌激素耐药 T47DCO 人乳腺癌细胞的生长抑制和胰岛素受体增加：对内分泌治疗的影响。
影响因子：
11.2
作者：
Horwitz,KB;Freidenberg,GR
通讯作者：
Freidenberg,GR
糖皮质激素介导的 α1-酸性糖蛋白诱导：激素调节 RNA 加工的证据。
DOI：
10.1073/pnas.81.14.4241
发表时间：
1984
影响因子：
11.1
作者：
Vannice,JL;Taylor,JM;Ringold,GM
通讯作者：
Ringold,GM