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

Kun Chun Chiang, Huang Yang Chen, Shu Yuan Hsu, Jong Hwei S. Pang, Shang Yu Wang, Jun Te Hsu, Ta Sen Yeh, Li Wei Chen, Sheng Fong Kuo, Chi Chin Sun, Jim Ming Lee, Chun Nan Yeh, Horng Heng Juang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

10 Scopus citations

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 or in combination with other drugs for ER+ breast cancer with PTEN insufficiency.

Original languageEnglish
Pages (from-to)4631-4638
Number of pages8
JournalDrug Design, Development and Therapy
Volume9
DOIs
StatePublished - 13 08 2015

Bibliographical note

Publisher Copyright:
© 2015 Chiang et al.

Keywords

  • Breast cancer
  • Cell cycle
  • MCF-7
  • PTEN
  • Target therapy
  • Tumor growth

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