PTEN insufficiency modulates ER+ breast cancer cell cycle progression and increases cell growth in vitro and in vivo

Drug Design, Development and Therapy
Kun-Chun ChiangHorng-Heng Juang

Abstract

Phosphatase and tensin homolog (PTEN), a well-known tumor suppressor gene and frequently mutated or lost in breast cancer, possesses the negative regulation function over the PI3K/Akt/mTOR pathway. PTEN insufficiency has been associated with advanced breast cancer and poor prognosis of breast cancer patients. Recently, target therapies aimed at PI3K/Akt/mTOR pathway to treat breast cancer have got popularity. However, the exact effect of PTEN on breast cancer cells is still not well understood. This study demonstrated that PTEN knockdown in MCF-7 cells strengthened the downstream gene expressions, including p-Akt, p-ERK1/2, p-mTOR, p-p70s6k, and p-GSK3β. PTEN knockdown MCF-7 cells had increased cell growth and Ki-67 expression. Further Western blot demonstrated that p27 was repressed obviously with p21 slightly inhibited and CDK1, 2, 4, 6, cyclin A, and Cdc25C were upregulated in MCF-7 PTEN knockdown cells, leading to the higher growth rate. More importantly, PTEN knockdown MCF-7 cells had higher tumorigenesis and tumor growth in vivo. From our current work, we provided more detailed PTEN-mediated mechanisms to stimulate ER+ breast cancer cell growth. Our result may pave the way for further target therapy development used alone...Continue Reading

Citations

Dec 1, 2017·International Journal of Molecular Sciences·Marilina García-Aranda, Maximino Redondo
Jul 22, 2017·Molecular Medicine Reports·Huijuan Liu, Hui Ye

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Methods Mentioned

BETA
PCR
xenografts
reverse transcription-PCR
flow cytometry
xenograft

Software Mentioned

CellQuestPro

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