The Study On Regulation Of Responsiviness To Endorcrine Therapy In Breast Cancer Cell MDA-MB-435

Background and Purpose To investigate chemically induced ERa expression in ERa negative human breast cancer cells MDA-MB-435 and restoration of it's responsiveness to endocrine therapy .Methods Human breast cells MDA-MB-435 were treated with HDAC inhibitor trichostatin A ( TSA ) and DNMT inhibitor 5-AZA-CdR (AZA ) . The mRNA expression of ERa, PR and PS2 in the treated MDA-MB-435 cells were detected by RT-PCR. The WST (water-soluble tetrazolium salt) methods were used to analyze the cells proliferation. FCM method was used to analyze the change of the distribution of stages of the treated cells.Results After treatment by the two chemicals, mRNA expression of ERa, PR and PS2 were up-regulated in MDA-MB-435. In the proliferation rate analysis :there are four treatment groups established : (1)vehicle (2) AZA+TSA (3) AZA+TSA +4-OH TAM(4)4-OH TAM. After treatment of the two chemicals,Group(2)(AZA+TSA)demonstrated down-regulated proliferation rate(P<0.01);the proliferation rate of Group(3)(AZA+TSA +4-OH TAM )were lower and the proliferation rate of Group (4)(4-OH TAM)showed no difference with the vehicle and the chemically treated MDA-MB-435 demonstrated different proliferation rate in the different concentration of 17β-estrodial . In the cell cycle analysis: there were four treatment groups established: (1)vehicle (2)AZA+TSA(3) AZA+TSA +E₂(4) AZA+TSA+E2+4-OH TAM. Group(2)(AZA+TSA) showed a S-stage arrest; Group (3)(AZA+TSA+E₂) showed a weaker S-stage arrest and Group(4) (AZA+TSA+E2+4-OH TAM) demonstrated a S-stage arrest with the same level as Group(2).Conclusion After treatment of TSA and AZA, ERα negative MDA-MB-435 cells can express functional ERa and become responsive to and dependent on estrogen in vivo and in vitro. HDAC inhibitor TSA and DNMT inhibitor AZA can suppress the proliferation of MDA-MB-435 and may play important roles in restoring sensitivity of the ERa negative breast cancer cell MDA-MB-435 to endocrine therapy.OBIECTIVE To compare the effects of breast conservative therapy (BCT) with modified radical mastectomy (MRM) in women with early stage breast cancer in the east part of China, METHODS AND PATIENTS we conducted a matched retrospective cohort study using data on patients derived from a prospectively collected breast cancer database. The database included patients who received MRM or BCT from 1995 to 2002 in our hospital. The match was conducted according with four variables: age at diagnosis, axillary lymph node status, hormone receptor status and the dimension of tumor. The match ratio was 1:2. Controls were patients who received MRM (n= 254). Cases were patients who received BCT (n=127). Median follow-up for the controls and cases were 58 months and 49 months respectively. The differences of incidence of loco-regional recurrence, disease free survival and overall survival at 5 years were compared. There were no significant differences in incidence of loco-regional recurrence, DFS and OS at 5 years between the two groups of patients.RESULTS The incidence of loco-regional recurrence was 1.84% in MRM group and 3.39% in BCT group (p=0.55). The DFS in MRM and BCT patients were 91.57% and 86.04% (p=0.37); the OS in MRM and BCT patient were 97.57% and 96.73% (p=0.66).CONCLUSION For appropriate breast cancer patients, classic lumpectomy plus axillary dissection and post-operative radiotherapy lead to excellent local controland good survival rate in our study. The BCT can result in the same effects as MRM in Chinese breast cancer patients with better cosmetic appearances.