PTEN sensitizes MDA-MB-468 cells to inhibition of MEK/Erk signaling for the blockade of cell proliferation

  • Authors:
    • Kibeom Jang
    • Minsoon Kim
    • Hye-Sook Seo
    • Incheol Shin
  • View Affiliations

  • Published online on: September 1, 2010     https://doi.org/10.3892/or_00000922
  • Pages: 787-793
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Abstract

Phosphatase and tensin homolog (PTEN) is a tumor suppressor that inhibits PI3K/Akt signaling. To examine the effect of PTEN on breast cancer cell proliferation, we expressed PTEN in MDA-MB-468 cells (MDA-MB-468 PTEN) by retroviral infection and tested the cell proliferation rate. We found that the growth rate of MDA-MB-468 PTEN cells was significantly lower than that of MDA-MB-468 control vector cells (MDA-MB-468 vec). When the PI3K/Akt signaling inhibitor LY294002 and the MEK/Erk signaling inhibitor U0126 were applied, LY294002 reduced cell proliferation in MDA-MB-468 PTEN and MDA-MB-468 vec by 20%, while U0126 led to a >60% reduction in MDA-MB-468 PTEN and a 20% reduction in MDA-MB-468 vec cells. FACS analysis demonstrated that the subG0/G1 apoptotic fraction was significantly increased in MDA-MB-468 PTEN cells after U0126 treatment, while LY294002 treatment in both cell lines and U0126 treatment in MDA-MB-468 vec cells led to a modest increase in the apoptotic fraction. This phenomenon was accompanied by the down-regulation of p-Erk. p-Erk levels were significantly lower after U0126 treatment in MDA-MB-468 PTEN cells. Similar results were observed in MDA-MB-231 cells, which express endogenous PTEN. The growth of MDA-MB-231 cells was significantly inhibited after U0126 treatment, compared to LY294002, while PTEN-null ZR-75-1 cells did not show increased sensitivity to U0126 over LY294002. Taken together, these findings suggest that blockade of PI3K/Akt signaling by PTEN may render breast cancer cells more dependent on the MEK/Erk pathway for their proliferation and survival.

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September 2010
Volume 24 Issue 3

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

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Spandidos Publications style
Jang K, Kim M, Seo H and Shin I: PTEN sensitizes MDA-MB-468 cells to inhibition of MEK/Erk signaling for the blockade of cell proliferation . Oncol Rep 24: 787-793, 2010.
APA
Jang, K., Kim, M., Seo, H., & Shin, I. (2010). PTEN sensitizes MDA-MB-468 cells to inhibition of MEK/Erk signaling for the blockade of cell proliferation . Oncology Reports, 24, 787-793. https://doi.org/10.3892/or_00000922
MLA
Jang, K., Kim, M., Seo, H., Shin, I."PTEN sensitizes MDA-MB-468 cells to inhibition of MEK/Erk signaling for the blockade of cell proliferation ". Oncology Reports 24.3 (2010): 787-793.
Chicago
Jang, K., Kim, M., Seo, H., Shin, I."PTEN sensitizes MDA-MB-468 cells to inhibition of MEK/Erk signaling for the blockade of cell proliferation ". Oncology Reports 24, no. 3 (2010): 787-793. https://doi.org/10.3892/or_00000922