Programmed cell death 4 inhibits leptin-induced breast cancer cell invasion

  • Authors:
    • Vianey González-Villasana
    • René Nieves-Alicea
    • Vanity McMurtry
    • Yolanda Gutiérrez-Puente
    • Ana M. Tari
  • View Affiliations

  • Published online on: December 21, 2011     https://doi.org/10.3892/or.2011.1600
  • Pages: 861-866
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Abstract

Obesity is a significant risk factor for post-menopausal women to develop and die from breast cancer. Leptin, an adipokine is produced in high levels in obese individuals, and its receptor is overexpressed in breast tumors and lymph node metastases. Previously, we demonstrated that leptin stimulates breast cancer cell invasion, which is correlated with breast cancer metastasis. Programmed cell death 4 (PDCD4) has been shown to block cancer cell invasion. However, whether PDCD4 blocks leptin-induced breast cancer cell invasion is not known. Here, we report the novel findings that leptin failed to induce invasion in MCF-7 breast cancer cells overexpressing PDCD4 (MCF-7/PDCD4). Tissue inhibitor of metalloproteinase-2 (TIMP-2) was essential to the anti-invasive effect of PDCD4, as leptin stimulated the invasion of MCF-7/PDCD4 cells pretreated with TIMP-2 siRNA. Furthermore, TIMP-2 knockdown allowed leptin to augment phosphorylation of extracellular signal-regulated kinases 1,2 and signal transducer and activator of transcription 3, but not that of Jun N-terminal kinases. These data indicate that PDCD4 utilizes TIMP-2 to exert its anti-invasive effect by suppressing leptin-induced activation of extracellular signal-regulated kinases 1,2 and signal transducer and activator of transcription 3. Novel therapeutic strategies aiming at enhancing PDCD4 expression in breast tumors may be able to stop obesity-related breast tumor progression and prolong the life of patients.

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March 2012
Volume 27 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
González-Villasana V, Nieves-Alicea R, McMurtry V, Gutiérrez-Puente Y and Tari AM: Programmed cell death 4 inhibits leptin-induced breast cancer cell invasion. Oncol Rep 27: 861-866, 2012.
APA
González-Villasana, V., Nieves-Alicea, R., McMurtry, V., Gutiérrez-Puente, Y., & Tari, A.M. (2012). Programmed cell death 4 inhibits leptin-induced breast cancer cell invasion. Oncology Reports, 27, 861-866. https://doi.org/10.3892/or.2011.1600
MLA
González-Villasana, V., Nieves-Alicea, R., McMurtry, V., Gutiérrez-Puente, Y., Tari, A. M."Programmed cell death 4 inhibits leptin-induced breast cancer cell invasion". Oncology Reports 27.3 (2012): 861-866.
Chicago
González-Villasana, V., Nieves-Alicea, R., McMurtry, V., Gutiérrez-Puente, Y., Tari, A. M."Programmed cell death 4 inhibits leptin-induced breast cancer cell invasion". Oncology Reports 27, no. 3 (2012): 861-866. https://doi.org/10.3892/or.2011.1600