Tamoxifen Caused The Down-regulating Of ARID1A, ERα And Up-regulating Of PR And P53in Endometrial Cancer Cells

Objective: Endometrial cancer is the most common malignant tumor infemale reproductive system, there are many factors associating with theoccurrence and development of endometrial cancer, such as long-timeestrogen stimulation without progesterone antagonist. The incidence of theendometrial cancer increased after tamoxifen（TAM） therapy. But thepossible pathogenesis of endometrial cancer are still unknown now. Currently,the researches of chromatin-remodeling complexes are progressively, some ofwhich shows that it plays an important role in tumor. ARID1A（AT-richinteracting domain containing protein） as one of the tumor suppressor genes,has mutated in varies tumors. We know more about the structure of ARID1A,while we know less about the characteristics and the function of ARID1A inendometrial cancer and the correlation of ARID1A with other genes relatingtumor. Here the experiment analysis the expressions of the genes and proteinsof ARID1A, ERα, ERβ, PR and P53in endometrial cancer cells treated bydifferent concentrations of TAM or estrogen E2at different time, Moreover,cell cycle analysis done by flow cytometry. The aim is trying to find the roleof ARID1A in the occurrence and development of endometrial cancer cells,and the possible mechanism of tamoxifen which lead to endometrial cancer.Methods:1The expression of ARID1A, ERα, ERβ, PR and P53mRNA in normalendometrium, high-grade endometrial cancer cells (Ishikawa), middle-gradeendometrial cancer cells (HEC-1A) and low-grade endometrial cancer cells(KLE) were detected by qRT-PCR.2The expressions of ARID1A, ERα, ERβ, PR and P53mRNA inendometrial cancer cells treated with different concentrations of TAM or E2atdifferent time respectively were detected by qRT-PCR. 3The expression of BAF250a, ERα, ERβ, PR and P53protein in normalendometrium, high-grade endometrial cancer cells (Ishikawa), middle-gradeendometrial cancer cells (HEC-1A) and low-grade endometrial cancer cells(KLE) were detected by Western-blot.4The expression of ARID1A, ERα, ERβ, PR and P53mRNA inendometrial cancer cells treated with different concentrations of TAM or E2atdifferent time respectively were detected by Western-blot.5The cell cycle of endometrial cancer cells treated with differentconcentrations of TAM or E2at different time respectively were detected byflow cytometric method (FCM).Results：1The expressions of ARID1A, ERα, ERβ, PR mRNA and protein inendometrial carcinoma cells were less than it in normal endometrium tissues.After treated by TAM or E2, the expressions of ARID1A, ERα, ERβ mRNAand protein reduced with the increase of drug concentration and the extensionof drug processing time (P <0.05), However, the expressions of PR and P53mRNA and protein increased with the increase of drug concentration and theextension of drug processing time(P <0.05);2After treated with different concentrations of TAM or E2at differenttime, G0/G1phase of endometrial cells gradually shortened, while S phaselengthened with the increase of concentration and time prolonged（P<0.05）.Conclusions:1. The expressions of ARID1A, ERα, ERβ mRNA and protein inendometrial cells treated with TAM or E2were much lower than thosewithout TAM or E2, while PR and P53mRNA and protein in endometrialcells treated with TAM or E2were higher than those without TAM or E2.2. TAM or E2may caused endometrial carcinoma by down-regulatingthe expressions of ARID1A which may be related to ER and P53.3. After the treatment of TAM or E2, G0/G1phase of endometrial cancer cells was shorten, while the S phase was lengthen.