Leptin utilizes Jun N-terminal kinases to stimulate the invasion of MCF-7 breast cancer cells
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In breast tumors, high levels of leptin have been associated with increased incidence of breast cancer metastasis. Breast cancer metastasis is directly associated with breast cancer cell invasion. However, whether leptin could augment breast cancer cell invasion is not known. Here we showed that leptin increased the invasiveness and the matrix metallo-proteinase-2 (MMP-2) activity of the MCF-7 breast cancer cell line. Leptin stimulated the phosphorylation of extracellular signals regulated kinases, signal transducers and activators of transcription 3 and Jun N-terminal kinases (JNK); however, only inhibition of JNK decreased leptin-mediated activation of MMP-2. Furthermore, inhibition of JNK suppressed leptin-mediated breast cancer cell invasion. Here we report the novel findings that leptin increased invasion of breast cancer cells by activating JNK, resulting in increased MMP-2 activity.
KeywordsBreast cancer invasion Extracellular signals regulated kinases Jun N-terminal kinases Leptin Matrix metallo-proteinase-2 Signal transducers and activators of transcription 3
Dulbecco’s Modified Eagle’s Medium/Nutrient Mixture F-12
Extracellular signals regulated kinases
Janus-activated kinase 2
Jun N-terminal kinases
Signal transducers and activators of transcription 3
This research was supported in part by the Cancer Research and Prevention Foundation (to A.-M. Simeone) and by the Susan G. Komen Breast Cancer Foundation (to A. M. Tari).
- 20.Chen C, Chang YC, Liu CL et al (2006) Leptin-induced growth of human ZR-75-1 breast cancer cells is associated with up-regulation of cyclin D1 and c-Myc and down-regulation of tumor suppressor p53 and p21WAF1/CIP1. Breast Cancer Res Treat 98:121–132. doi:10.1007/s10549-005-9139-y PubMedCrossRefGoogle Scholar
- 21.Saxena NK, Vertino PM, Anania FA et al (2007) Leptin-induced growth stimulation of breast cancer cells involves recruitment of histone acetyltransferases and mediator complex to CYCLIN D1 promoter via activation of Stat3. J Biol Chem 282:13316–13325. doi:10.1074/jbc.M609798200 PubMedCrossRefGoogle Scholar
- 25.Cleary MP, Juneja SC, Phillips FC et al (2004) Leptin receptor-deficient MMTV-TGF-alpha/Lepr(db)Lepr(db) female mice do not develop oncogene-induced mammary tumors. Exp Biol Med (Maywood) 229:182–193Google Scholar
- 46.Ogunwobi O, Mutungi G, Beales IL (2006) Leptin stimulates proliferation and inhibits apoptosis in Barrett’s esophageal adenocarcinoma cells by cyclooxygenase-2-dependent, prostaglandin-E2-mediated transactivation of the epidermal growth factor receptor and c-Jun NH2-terminal kinase activation. Endocrinology 147:4505–4516. doi:10.1210/en.2006-0224 PubMedCrossRefGoogle Scholar