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Breast Cancer Research and Treatment

, Volume 119, Issue 3, pp 559–574 | Cite as

Glypican-3 reexpression regulates apoptosis in murine adenocarcinoma mammary cells modulating PI3K/Akt and p38MAPK signaling pathways

  • C. Buchanan
  • I. Stigliano
  • H. M. Garay-Malpartida
  • L. Rodrigues Gomes
  • L. Puricelli
  • M. C. Sogayar
  • E. Bal de Kier Joffé
  • M. G. Peters
Preclinical Study

Abstract

Glypican-3 (GPC3) is a proteoglycan involved in proliferation and cell survival. Several reports demonstrated that GPC3 is downregulated in some tumors, such as breast cancer. Previously, we determined that GPC3 reexpression in the murine mammary adenocarcinoma LM3 cells induced an impairment of their invasive and metastatic capacities, associated with a decrease of their motility and an increase of their cell death. We demonstrated that GPC3 inhibits canonical Wnt signaling, as well as it activates non canonical pathway. Now, we identified signaling pathways responsible for the pro-apoptotic role of GPC3 in LM3 cells. We found for the first time that GPC3 inhibits the PI3K/Akt anti-apoptotic pathway while it stimulates the p38MAPK stress-activated one. We report a concomitant modulation of CDK inhibitors as well as of pro- and anti-apoptotic molecules. Our results provide new clues regarding the mechanism involved in the modulation induced by GPC3 of mammary tumor cell growth and survival.

Keywords

Glypican-3 Apoptosis PI3K/Akt pathway p38MAPK pathway Breast cancer 

Notes

Acknowledgments

We would like to give our thanks to Guillermo Peluffo for technical assistance and to Dr. Mariana Salatino for her invaluable assistance in responding the reviewer requests. The work was supported by grants from FONCyT (PICT 14088, Préstamo BID 1728/OC-AR; PICT 00220, Préstamo BID 1728/OC-AR) and from the University of Buenos Aires (UBACyT M068).

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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • C. Buchanan
    • 1
  • I. Stigliano
    • 1
  • H. M. Garay-Malpartida
    • 2
  • L. Rodrigues Gomes
    • 3
  • L. Puricelli
    • 1
  • M. C. Sogayar
    • 3
  • E. Bal de Kier Joffé
    • 1
  • M. G. Peters
    • 1
  1. 1.Cell Biology Department, Research Area, Institute of Oncology “Angel H. Roffo”University of Buenos AiresBuenos AiresArgentina
  2. 2.School of Arts, Sciences and HumanitiesUniversity of São PauloSão PauloBrazil
  3. 3.Chemistry InstituteUniversity of São PauloSão PauloBrazil

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