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Gyesik Min 생화학분자생물학회 2010 Experimental and molecular medicine Vol.42 No.11
The nuclear receptors, steroid and xenobiotic receptor (SXR) and constitutive androstane receptor (CAR) play important functions in mediating lipid and drug metabolism in the liver. The present study demonstrates modulatory actions of estrogen in transactivations of SXR-mediated liver X receptor response element (LXRE) and CAR-mediated phenobarbital response element (PBRU). When human estrogen receptor (hERα)and SXR were exogenously expressed, treatment with either rifampicin or corticosterone promoted significantly the SXR-mediated transactivation of LXRE reporter gene in HepG2. However, combined treatment with estrogen plus either rifampicin or corticosterone resulted in less than 50% of the mean values of the transactivation by rifampicin or corticosterone alone. Thus, it is suggested that estrogen may repress the SXR-mediated transactivation of LXRE via functional cross-talk between ER and SXR. The CAR-mediated transactivation of PBRU was stimulated by hERα in the absence of estrogen. However, the potentiation by CAR agonist, TCPOBOP, was significantly repressed by moxestrol in the presence of ER. Thus, ER may play both stimulatory and inhibitory roles in modulating CAR-mediated transactivation of PBRU depending on the presence of their ligands. In summary, this study demonstrates that estrogen modulates transcriptional activity of SXR and CAR in mediating transactivation of LXRE and PBRU, respectively, of the nuclear receptor target genes through functional cross-talk between ER and the corresponding nuclear receptors.
Gyesik Min(민계식) 한국생명과학회 2011 생명과학회지 Vol.21 No.12
이 연구는 에스트로겐, 프로게스테론 및 타목시펜의 각각 다른 농도와 처리기간에 따라 배양된 사람 난소유래 암세포주인 HeLa 세포의 증식에 미치는 영향을 MTT 분석에 의해 조사하였다. 에스트로겐은 2.5~6일의 처리기간동안 1 ㎍/ml의 농도까지는 세포증식에 영향을 주지 않았지만, 더 높은 10 ㎍/ml의 농도에서는 처리기간의 증가에 따라 점진적으로 현저하게 세포증식을 억제하였다. 또한 10 ㎍/ml 농도 이상의 프로게스테론을 2.5일 동안 처리할 경우 HeLa 세포의 증식을 현저하게 억제하였으며, 4일 동안 처리시에는 농도-의존성 억제효과를 나타내었다. 그러나, 6일 동안 더 장기간의 프로게스테론 처리는 4일 동안의 처리기간에서 관찰된 세포증식에 대한 농도-의존성 억제효과를 제거하였다. 그리고, 타목시펜은 HeLa 세포주의 증식에 대한 억제효과를 위하여 에스트로겐보다 더 높은 농도(100 ㎍/ml)를 필요로 하였다. 이러한 결과는 고농도의 에스트로겐, 프로게스테론 그리고 타목시펜이 HeLa 세포의 증식을 억제할 뿐만 아니라, 농도 및 처리기간 또한 세포증식에 대한 억제효과에 영향을 미칠 수 있음을 제시한다. This study examined the effects of estrogen, progesterone and tamoxifen at different concentrations and treatment periods on proliferation of a human cervical carcinoma cell line, HeLa, in culture, based on MTT assay. Estrogen did not have an effect on the cellular proliferation in concentrations up to 1 ㎍/ml for treatment periods of between 2.5 and 6 days, but significantly inhibited proliferation at a higher concentration of 10 ㎍/ml in a progressive manner with increasing treatment periods. Also, treatment of HeLa with more than 10 ㎍/ml of progesterone for 2.5 days significantly inhibited proliferation and caused a concentration-dependent inhibition with 4 days of treatment. However, longer treatment with progesterone for 6 days abolished the concentration-dependent inhibitory effect on cellular proliferation observed with the 4-day treatment period. Furthermore, tamoxifen required a higher concentration (100 ㎍/ml) than estrogen to bring about the inhibitory effect on the HeLa proliferation. These results suggest that high concentrations of estrogen, progesterone and tamoxifen may suppress proliferation of HeLa, and both the concentration and the treatment period may also influence their inhibitory effects on cellular proliferation.