Gene expression profiling of the androgen independent prostate cancer cells demonstrates complex mechanisms mediating resistance to docetaxel

Desarnaud, Frank; Geck, Peter; Parkin, Christopher; Carpinito, Gino; Makarovskiy, Andrew

doi:10.4161/cbt.11.2.13750

Cited by 24 publications

(29 citation statements)

References 35 publications

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“…The authors also compared DU-145 with docetaxel-resistant DU-145 cells and showed a set of 10 genes present in both PC-3R and DU-145R cells (19). However, in contrast to our study only LAMC2, which increases more than 10% during hormone escape in prostate cancer (48), was represented in both models.…”

Section: Log Ratiocontrasting

confidence: 63%

Identification of Docetaxel Resistance Genes in Castration-Resistant Prostate Cancer

Marín-Aguilera

Codony-Servat

Kalko

et al. 2012

Molecular Cancer Therapeutics

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Docetaxel-based chemotherapy is the standard first-line therapy in metastatic castration-resistant prostate cancer (CRPC). However, most patients eventually develop resistance to this treatment. In this study, we aimed to identify key molecular genes and networks associated with docetaxel resistance in two models of docetaxelresistant CRPC cell lines and to test for the most differentially expressed genes in tumor samples from patients with CRPC. DU-145 and PC-3 cells were converted to docetaxel-resistant cells, DU-145R and PC-3R, respectively. Whole-genome arrays were used to compare global gene expression between these four cell lines. Results showed differential expression of 243 genes (P < 0.05, Bonferroni-adjusted P values and log ratio > 1.2) that were common to DU-145R and PC-3R cells. These genes were involved in cell processes like growth, development, death, proliferation, movement, and gene expression. Genes and networks commonly deregulated in both DU-145R and PC-3R cells were studied by Ingenuity Pathways Analysis. Exposing parental cells to TGFB1 increased their survival in the presence of docetaxel, suggesting a role of the TGF-b superfamily in conferring drug resistance. Changes in expression of 18 selected genes were validated by real-time quantitative reverse transcriptase PCR in all four cell lines and tested in a set of 11 FFPE and five optimal cutting temperature tumor samples. Analysis in patients showed a noteworthy downexpression of CDH1 and IFIH1, among others, in docetaxel-resistant tumors. This exploratory analysis provides information about potential gene and network involvement in docetaxel resistance in CRPC. Further clinical validation of these results is needed to develop targeted therapies in patients with CRPC that can circumvent such resistance to treatment.

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Section: Log Ratiocontrasting

confidence: 63%

Identification of Docetaxel Resistance Genes in Castration-Resistant Prostate Cancer

Marín-Aguilera

Codony-Servat

Kalko

et al. 2012

Molecular Cancer Therapeutics

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“…The authors critically evaluated the panel of genes deregulated between parent (docetaxel-sensitive) and sub-clone (docetaxel-resistant) and found that few genes met their criteria for deregulation. 1 However, the biological functions to which some genes annotated made sense in terms of resistance to docetaxel. The presented data do not convince us that these genes might be useful for predicting resistance, although this was not their described goal.…”

Section: O N O T D I S T R I B U T Ementioning

confidence: 99%

“…Thus, Finally, the authors report that a single gene of unknown function, FAM83A was concordantly overexpressed in the two resistant cell line clones. 1 Functional characterization of this gene using ectopic expression in the resistant clones and determination of changes in sensitivity to docetaxel may well provide unexpected information that anchors the control of gene expression, biological function and response to therapy.…”

Section: O N O T D I S T R I B U T Ementioning

confidence: 99%

“…1 Of the three genes evaluated, only cyclin G 2 ablation rescues sensitivity to docetaxel in the PC-3 resistant clones. Previously, Bates and colleagues describe cyclin G 2 as a DNA damage inducible gene.…”

mentioning

confidence: 99%

“…In the accompanying article by Desarnaud and colleagues, the authors utilize gene expression data to explore mechanisms of resistance to docetaxel in androgen-independent prostate cancer cells. 1 Gene expression data derived from multiple docetaxel-resistant clones were compared with the data derived from docetaxel-sensitive parental lines. The authors found that the gene expression patterns in resistant clones of PC3 cells or DU-145 cells suggested deregulation of programs involving cell growth, metabolic functions, cell structure and communication.…”

mentioning

confidence: 99%

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