Abstract
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.
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Abbreviations
- DMEM/F-12:
-
Dulbecco’s Modified Eagle’s Medium/Nutrient Mixture F-12
- ERK:
-
Extracellular signals regulated kinases
- JAK2:
-
Janus-activated kinase 2
- JNK:
-
Jun N-terminal kinases
- MMPs:
-
Metalloproteinases
- SRC:
-
Sarcoma oncogene
- STAT3:
-
Signal transducers and activators of transcription 3
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Acknowledgments
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).
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McMurtry, V., Simeone, AM., Nieves-Alicea, R. et al. Leptin utilizes Jun N-terminal kinases to stimulate the invasion of MCF-7 breast cancer cells. Clin Exp Metastasis 26, 197–204 (2009). https://doi.org/10.1007/s10585-008-9231-x
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DOI: https://doi.org/10.1007/s10585-008-9231-x