Expression Of Activating Transcription Factor 3 In Uterine Serous Carcinoma And Effection On Proliferation Of SPEC-2 In Vitro

BackgroundEndometrial carcinoma (also called corpus carcinoma) is a gynecological malignancy that arises from the endometrium and mainly affects the perimenopausal and aged women. There are three major subtypes of endometrial cancer:Type I is the hormone-dependent endometrioid adenocarcinoma; Type II is non-hormonal dependent, including the serous carcinoma and clear cell carcinoma of the endometrium; Type III is an autosomal dominant genetic disease, the Lynch syndrome. Among these subtypes, serous carcinoma only comprises 10% of all cases of endometrial carcinoma, however it is responsible for over 50% of the overall mortality. A systematic understanding of the clinicopathological features, diagnosis, differential diagnosis and prognosis of uterine serious carcinoma (USC) would greatly benefit the work of gynecologists, oncologists and pathologists.Objects:To discuss the clinicopathological features, the differential diagnosis and prognosis of endometrial serous carcinoma (USC). Methods:The clinical information of 33 patients aged 44-73 years old admitted to Yantai Huhuangding hospital for surgical treatment of USC between Jan 2005 and Dec 2013 were retrospectively reviewed. Immunohistochemistry analysis of ER, PR and MTP53 markers were performed and their correlation with the clinical features and prognosis of USC were studied and discussed. Results:USC comprised 5.02% of all cases of endometrial carcinoma and mostly affected postmenopausal women with postmenopausal vaginal bleeding or vaginal discharge as the main symptom. Imageological tests mostly showed intrauterine space occupying lesions.81.82% of the cases were ER-/PR-and 72.73% were MTP53+. Expression of ER, PR and MTP53 markers were not significantly different among different age group, tumor sizes, infiltration depth, tumor staging and metastasis. P53 mutation might be closely related to the tumorigenesis of USC and lymphatic metastasis was a predictive factor for poor prognosis. Conclusion:This study provided us a better understanding of this rare type of carcinoma and could benefit future works of gynecologists, oncologists and pathologists.BackgroundEndometrial cancer (also called corpus carcinoma) is a gynecological cancer that arises from the endometrium and mainly affects the perimenopausal and aged women. Endometrial cancer, cervical cancer and ovarian cancer are the three major malignancies in female reproductive system. The morbidity and mortality rate of endometrial cancer have been increasing in recent years across the world and the onset age tends to be younger. Uterine serous carcinoma (USC) is a special pathological type of high-aggressive endometrial cancer. Although the incidence of USC only comprises 10% of total endometrial carcinomas, its high malignant degree makes the five-year survival rate to be much lower than endometrioid adenocarcinoma.Previous studies have identified the close involvement of p53 mutation in the occurrence of serous carcinoma. Multiple proteins have been found to regulate the function of mutant type p53 (MTP53) by affecting its conformation or promote protein degradation, therefore suppressing tumorigenesis or metastasis. Activating Transcription Factor 3 (ATF3) protein is an important regulatory factor for wild-type p53 (WTP53). Binding of ATF3 to WTP53 induces the change in WTP53 conformation, making it easier to bind to DNA sequences or other transcription activating factors. ATF3 also competitively binds to the promoter region of p53, enhancing its transcriptional activity. In vitro studies revealed that ATF3 could directly bind to and repress the activity of MTP53. ATF3 has been shown to function as a tumor suppressor in bladder cancer and colon cancer. Other studies reported a significant reduce of ATF3 expression in many tumor tissues, including lung cancer, breast cancer and liver cancer, suggesting its role in tumorigenesis. However, the involvement of ATF3 in USC was not clear. In this study, we investigated the expression profile of ATF3 in USC and its relationship with MTP53, and discussed the possible mechanism of ATF3 in tumorigenesis of USC. Our research might provide a novel target for treating USC.Objects:To investigate the expression of ATF3, its correlation with MTP53 in uterine serous carcinoma, and discuss the possible mechanism of its significance in this neoplasm. Methods:The clinical information of 33 patients aged 44-73 years old admitted to Yantai Yuhuangding hospital for surgical treatment of USC between Jan 2005 and Dec 2013 were retrospectively reviewed. Immunohistochemistry analysis of ATF3 and MTP53 were performed on USC and surrounding tissues. Correlation between ATF3 expression and the clinicopathological features of patients, MTP53 expression and disease-free survival of patients were analyzed. Results:The positive ratio of ATF3 stain in USC and adjacent tissues among all 33 patients was 27.27% (7/33) and 87.88% (29/33) respectively, which was significantly different (P<0.01). There was no significant difference in ATF3 positive ratio among each clinicopathological groups. We found a negative correlation between the ATF3 and MTP53 expression in USC tissues. The disease-free survival rate for ATF3+ve patients was significantly higher than in ATF3-ve patients. Conclusions:ATF3 plays an important role in the tomorigenesis of USC and is likely to be a prognostic factor for USC.BackgroundUterine serous carcinoma is one kind of endometrial cancer with special biological behavior which has a high degree of malignancy accounting for 50% of all endometrial cancer. There is still no effective treatment method. In the second part, the results indicated that the expression of ATF3 in USC tissues was lower and the expression of ATF3 was negatively correlated with the expression of MTP53. In this part of the experiment, the expression level of ATF3 in SPEC-2 cells was up-regulated. The effect of ATF3 on the proliferation of SPEC-2 and the mechanism in vitro was studied.Objects:To investigate the effects of ATF3 up-regulation on the proliferation of human uterine serous carcinoma line SPEC-2 and its mechanism. Methods: Ampho-293 and HEK-293Fast cells were used to prepare the virus. SPEC-2 cells were infected by Polybrene. Western Blot experiments were used to verify the success of transfection. The proliferation of cells was detected by MTT method. At different time points, the absorbance of the cells was detected at the wavelength of 490nm at the enzyme linked immunosorbent assay. The expression of MTP53, ATF3, P21 and CyclinDl in the cells was detected by Western Blot. Results:In negative control group and blank control group, the expression of ATF3 cells was lower in SPEC-2 cells, while the expression of ATF3 protein in the transfection group was significantly higher (P<0.05).The results of MTT showed that the growth rate of SPEC-2 cells was significantly lower than that in the control group. From the experimental results, it can be seen that the expression level of P21 increased, while the expression of MTP53 and CyclinDl decreased significantly (P<0.05). Conclusions:High expression of ATF3 in SPEC-2 cells could inhibit the proliferation in vitro. The expression of P21 was actived and the expression of mutant type P53 and CyclinD1 was inhibited might be the molecular mechanism of inhibition of cell proliferation.