Inhibition of AP-1 suppresses cervical cancer cell proliferation and is associated with p21 expression
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Michelle F. Maritz
Abstract
AP-1, a transcription factor comprised primarily of Jun and Fos family proteins, regulates genes involved in proliferation, differentiation and oncogenesis. Previous studies demonstrated that elevated expression of Jun and Fos family member proteins is associated with numerous human cancers and in cancer-relevant biological processes. In this study we used a dominant-negative mutant of c-Jun, Tam67, which interferes with the functional activity of all AP-1 complexes, to investigate the requirement of AP-1 in the proliferation and cell cycle progression of cervical cancer cells. Transient and stable expression of Tam67 in CaSki cervical cancer cells resulted in decreased AP-1 activity that correlated with a significant inhibition of cell proliferation and anchorage-independent colony formation. Inhibiting AP-1 activity resulted in a two-fold increase in cells located in the G2/M phase of the cell cycle and an accompanying increase in the expression of the cell cycle regulatory protein, p21. The increase in p21 was associated with a decrease in HPV E6 expression and an increase in p53. Importantly, blocking the induction of p21 in CaSki-Tam67-expressing cells accelerated their proliferation rate to that of CaSki, implicating p21 as a key player in the growth arrest induced by Tam67. Our results suggest a role for AP-1 in the proliferation, G2/M progression and inhibition of p21 expression in cervical cancer.
©2011 by Walter de Gruyter Berlin New York
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Articles in the same Issue
- Review
- Recent insights into regulation of transcription by RNA polymerase III and the cellular functions of its transcripts
- Genes and Nucleic Acids
- Post-transcriptional regulation of human cathepsin L expression
- Protein Structure and Function
- In vitro conversion and seeded fibrillization of posttranslationally modified prion protein
- Synthesis of recombinant high density lipoprotein with apolipoprotein A-I and apolipoprotein A-V
- Screening for small molecule modulators of Hsp70 chaperone activity using protein aggregation suppression assays: inhibition of the plasmodial chaperone PfHsp70-1
- Molecular Medicine
- Inhibition of AP-1 suppresses cervical cancer cell proliferation and is associated with p21 expression
- STAT3 controls matrix metalloproteinase-1 expression in colon carcinoma cells by both direct and AP-1-mediated interaction with the MMP-1 promoter
- Cell Biology and Signaling
- TGFβ1 suppresses vascular smooth muscle cell motility by expression of N-cadherin
- Renal pro-apoptotic proteins are reduced by growth hormone resistance but not by visceral fat removal
- Proteolysis
- Inhibition of Staphylococcus aureus cysteine proteases by human serpin potentially limits staphylococcal virulence
