Effect of Leptin on Growth of Breast Cancer Cells
Date Issued
2004
Date
2004
Author(s)
Chang, Yuan-Ching
DOI
zh-TW
Abstract
Breast cancer is the most prevalent malignant tumor in women and accounting for leading cause of cancer death among women. Obesity has been recognized as a risk factor for many cancers including breast cancer. The adipocyte represents one of the most abundant cell types surrounding breast cancer cells and the cytokines secreted from adipocytes may prove to be players in a paracrine manner. Leptin is an adipocyte derived cytokine. Leptin and leptin receptors expression has also been detected in normal and tumoral human mammary epithelial cells. Besides the classical function in regulating food intake and body weight, leptin may play a putative role in breast cancer cell growth through an autocrine and paracrine mechanism. By cell counting, MTT assay and Brdu incorporation, we demonstrated cell growth with leptin treatment in ZR-75-1 cells and T-47 D cells. Semiquantitative RT-PCR, Western blotting were use to detect the expression of specific proteins and transcription factors responsible to regulate the cell proliferation. We first found that c-myc, the oncogen from the hell, was upregulated following leptin exposure. We also confirmed theat cyclin D, the possible converge target of oncogenic pathway of estrogen and HER-2/neu, was also upregulated. At the same time, leptin could drive cell cycle progression by downregulation of expression of p53 and p21. Important findings are now emerging that give hope for the development of candidate drug molecules that are directed against a specific oncoprotein. We propose that leptin is a direct stimulating agent in breast cancer growth and play important role in “fail safe mechanism” of breast cancer when treated with antiestrogen and monoclonal antibody to HER-2/neu receptor (trastuzumab). Consequently, the leptin pathway should be further studied as a target for interventions to treat and/or prevent breast cancer.
Subjects
乳癌
瘦體素
leptin
breast cancer
SDGs
Type
text
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