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In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
Endogenous tumor suppression mediated by PTEN involves survivin gene silencing
Minakshi Guha1, Janet Plescia, Irwin Leav
1Department of Cancer Biology, Prostate Cancer Discovery and Development Program, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Cancer Research
|May 28, 2009
Summary
The tumor suppressor PTEN silences survivin gene expression, a key step in preventing cancer. This pathway, independent of p53, is crucial for endogenous tumor suppression and involves FOXO transcription factors.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Endogenous tumor suppression is vital against oncogenesis but its molecular mechanisms remain unclear.
- PTEN (phosphatase and tensin homolog) is a tumor suppressor gene frequently altered in human cancers.
- Survivin is an essential regulator of cell division and apoptosis, often overexpressed in cancer.
Purpose of the Study:
- To elucidate the molecular requirements of endogenous tumor suppression mediated by PTEN.
- To investigate the role of PTEN in regulating survivin expression.
- To understand the pathway linking PTEN, survivin, and oncogenesis.
Main Methods:
- Investigated the PTEN-survivin interaction in cancer cells.
- Utilized conditional PTEN deletion in mouse prostate models.
- Analyzed survivin and PTEN expression correlation in human cancer patients.
- Examined the role of FOXO1 and FOXO3a transcription factors in survivin promoter occupancy.
Main Results:
- PTEN directly silences survivin gene expression, independent of p53.
- This repression involves active transcriptional silencing of survivin.
- FOXO1 and FOXO3a directly bind to the survivin promoter.
- Conditional PTEN deletion in mice leads to survivin induction before tumor formation.
- Survivin and PTEN expression are inversely correlated in human cancer patients.
Conclusions:
- Silencing survivin is an essential function of endogenous PTEN tumor suppression.
- The PTEN-FOXO-survivin pathway represents a critical mechanism in preventing cancer development.
- Understanding this pathway offers potential therapeutic targets for cancer treatment.
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