Dissertation > Excellent graduate degree dissertation topics show

Mechanism of Leptin Interfering the Inhibition Growth Effect of Tamoxifen in MCF-7 Breast Cancer Cells

Author: ZhuZuoZuo
Tutor: YinYongMei
School: Nanjing Medical University
Course: Oncology
Keywords: breast cancer leptin tamoxifen ERα
CLC: R737.9
Type: Master's thesis
Year: 2011
Downloads: 25
Quote: 0
Read: Download Dissertation

Abstract

Purpose:Obesity is a risk factor for breast cancer and is associated with poor prognosis. Leptin, the protein product of the obese gene which could regulate energy metabolism. As a peptide hormone, it have been reported to play an important role in invasion and progression of various malignant tumors and the drug resistance of chemotherpy. This study was conducted to detect the expression of leptin receptor in breast cancer cell line MCF-7 and to investigate the role of leptin on cell proliferation as well as the mechanism of leptin interfering the inhibition growth effect of tamoxifen in MCF-7.Methods:MCF-7 was detected for OBR by immunofluorescence and Western blot. MCF-7 cells were treated with 100 ng/ml of leptin and 1000 nM of tamoxifen, MTT was used to detect cell proliferation and the levels of ERαwere detected by immunofluorescence and Western blot before and after drug treatment; Synthethesized the core fragment of human estrogen response element (ERE), and inserted it into pGL3-promoter vector multiple cloning sites in order to construct ERE reporter gene plasmid pERE-LUC. The plasmid was transiently transfected into MCF-7 cells, after leptin and tamoxifen treatment, detected the expression of luciferase, in order to investigate the impact of leptin on the transcriptional activity of ERα.Results:OBR was significantly overexpressed in MCF-7 cells. LEP could induce the proliferation of MCF-7 cells, and the concentration of 100 ng/ml LEP has the most obvious effect on cell proliferation( P<0.05); Contrarily, TAM could inhibit cell proliferation in a concentration dependent manner, 1000 nM has a significantly inhibitory effect( P<0.05), and the inhibition role of cell proliferation was reversed when LEP combined to TAM( P<0.05); LEP can increase the expression level of ERα, especially the nuclei level; Compared with LEP, TAM can decrease the expression level of ERα, with the combination of LEP, the effects of TAM on ERαis significantly antagonized( P<0.05). We constructed a plasmid which containing estrogen response element (ERE) reporter gene, and transfected it into MCF-7 cells, results indicated that E2 significantly stimulated the transcription of ERαabove the basal level, whereas the addition of TAM to E2 abolished this effect. LEP is also able to increase the transcriptional activity of ERα, the addition of TAM could significantly decrease the levels, the addition of leptin can apparently reverse the inhibition activity of TAM on ERα( P<0.05).Conclusion:LEP could interferes the impacts of TAM on breast cancer cells, leptin may contribute to the efficacy endocrine therapy of tamoxifen of breast cancer patients.

Mechanism of Leptin Interfering the Inhibition Growth Effect of Tamoxifen in MCF-7 Breast Cancer Cells

Abstract

Related Dissertations