Abstract
Classic mechanisms of tumor response to chemotherapy include apoptosis and mitotic catastrophe. Recent studies have suggested that cellular senescence, a terminal proliferation arrest seen in vitro, may be invoked during the exposure of cancer cells to chemotherapeutic agents. To identify markers associated specifically with the cellular senescence phenotype, we utilized expression data from cDNA microarray experiments identifying transcripts whose expression levels increased as human prostate epithelial cells progressed to senescence. When screened against other growth-inhibitory conditions, including quiescence and apoptosis, many of these transcripts were also upregulated, indicating that similar pathways occur between apoptosis and senescence. A senescent-like phenotype was then induced in several prostate cancer cell lines using 5-aza-2′-deoxycytidine, doxorubicin, or Docetaxel. Treatment with these agents resulted in a significant increase in the induction of senescence-specific genes when compared to nonsenescent conditions. The performance of the panel was improved with fluorescence-activated cell sorting using PKH26 to isolate nonproliferating, viable, drug-treated populations, indicating that a heterogeneous response occurs with chemotherapy. We have defined an RNA-based gene panel that characterizes the senescent phenotype induced in cancer cells by drug treatment. These data also indicate that a panel of genes, rather than one marker, needs to be utilized to identify senescence.
Original language | English |
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Pages (from-to) | 816-823 |
Number of pages | 8 |
Journal | Neoplasia |
Volume | 7 |
Issue number | 9 |
DOIs | |
State | Published - Sep 2005 |
Bibliographical note
Funding Information:Abbreviations: SA-b-gal, senescence-associated b-galactosidase; HPEC, human prostate epithelial cell; QPCR, quantitative reverse transcriptase polymerase chain reaction; FACS, fluorescence-activated cell sorting; DAC, 5-aza-2V-deoxycytidine Address all correspondence to: David F. Jarrard, MD, University of Wisconsin Comprehensive Cancer Center, 600 Highland Avenue, K6/530, Madison, WI 53792. E-mail: [email protected] 1This work was supported by The Prostate Foundation (formerly CapCURE) and the National Institutes of Health (CA76184 and CA97131). 2Steven R. Schwarze and Vivian X. Fu have contributed equally to this work. Received 15 March 2005; Revised 16 May 2005; Accepted 16 May 2005.
Keywords
- Cancer
- Cancer therapy
- Differentiation
- Prostate
- Senescence
ASJC Scopus subject areas
- Cancer Research