AP-1 blockade in breast cancer cells causes cell cycle arrest by suppressing G1 cyclin expression and reducing cyclin-dependent kinase activity

Oncogene
Yongmin LiuPowel H Brown

Abstract

The AP-1 transcription factor is a central component of signal transduction pathways in many cells, although the exact role of AP-1 in controlling cell growth and malignant transformation is unknown. We have previously shown that AP-1 complexes are activated by peptide and steroid growth factors in both normal and malignant breast cells, and that blocking AP-1 by overexpressing a dominant-negative form of cJun (cJun-DN, TAM67) inhibits breast cancer cell growth both in vivo and in vitro. We hypothesized that TAM67 inhibits cell growth by altering the expression of cell cycle regulatory proteins, thus causing a cell cycle block. In the present study, we used clones of MCF7 breast cancer cells that express TAM67 under the control of an inducible promoter. First, we determined the effect of AP-1 blockade on cell growth, then we performed 3H-thymidine incorporation and flow cytometry assays to investigate whether TAM67 inhibits the cell cycle. We observed that in the presence of serum TAM67 inhibited cell growth and caused a block in the G1 phase of the cell cycle. Next, we performed Western-blotting and CDK kinase assays to determine the effects of TAM67 on retinoblastoma (Rb) phosphorylation, the expression of cell cycle regulato...Continue Reading

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Citations

May 7, 2009·Breast Cancer Research and Treatment·Tyler LahusenAnna T Riegel
Jul 20, 2005·Oncogene·Chunhua LuPowel H Brown
Jan 8, 2010·The Journal of Biological Chemistry·Xuanmao JiaoRichard G Pestell
Nov 4, 2008·TheScientificWorldJournal·Thomas Schmitz, Li-Jin Chew
Aug 26, 2010·Molecular Cancer Research : MCR·Stanislav ZelivianskiJacqueline S Jeruss
Aug 19, 2010·Cancer Prevention Research·Jay W TichelaarMing You
Dec 3, 2011·Breast Cancer Research : BCR·Narendra V SankpalWilliam E Gillanders
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Oct 29, 2015·Mediators of Inflammation·Ting LiuHeping Yang
Jun 16, 2015·The Journal of Clinical Investigation·Jing ZhaoPowel H Brown
May 9, 2006·Developmental Biology·Qiang ShenPowel H Brown
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May 17, 2014·Journal of Medicinal Chemistry·Na YeJia Zhou
Jun 22, 2017·ACS Chemical Biology·Daniel BaxterJody M Mason

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