Differences in gene expression in prostate cancer, normal appearing prostate tissue adjacent to cancer and prostate tissue from cancer free organ donors

Chandran, Uma; Dhir, Rajiv; Ma, Changqing; Michalopoulos, George K.; Becich, Michael J.; Gilbertson, John D.

doi:10.1186/1471-2407-5-45

Cited by 135 publications

(114 citation statements)

References 31 publications

(29 reference statements)

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“…This revealed a slightly lower expression of endogenous SIM2s in the human prostate carcinoma DU145 cells compared with other prostate and pancreatic carcinoma cell lines (Figure 1a). Consequently, independently derived polyclonal cell pools showing stable ectopic expression of carboxy-terminal myc-tagged human SIM2s (SIM2s.myc) were generated in DU145 cell line to emulate an aberrant increase in SIM2s in prostate cancers compared with benign samples, as previously observed from several studies by others (Su et al, 2002;Chandran et al, 2005;Halvorsen et al, 2007). Puromycin-resistant control (Control) pools were generated by incorporation of the empty expression vector.…”

Section: Identification Of Bnip3 As a Putative Target Of Repression Bmentioning

confidence: 93%

“…Although the focus has mainly been on SIM2s in these tumour types, SIM2l messenger RNA (mRNA) has also been found to be expressed in tumours and tumour-derived cell lines of the pancreas (DeYoung et al, 2003b) and in prostate tumours (Halvorsen et al, 2007), but not in the corresponding normal cell lines or benign tissue samples. Several independent microarray studies have found SIM2 to be the second most consistently up-regulated gene in prostate tumours, while not being expressed in the corresponding benign tissue (Su et al, 2002;Chandran et al, 2005;Halvorsen et al, 2007). SIM2 over-expression in human pancreatic carcinoma samples and derived cell lines compared with normal ductal epithelium controls has also recently been found in the most comprehensive genome-wide analysis to date (Jones et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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The HIF1α-inducible pro-cell death gene BNIP3 is a novel target of SIM2s repression through cross-talk on the hypoxia response element

Farrall

Whitelaw

2009

Oncogene

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The short isoform of single-minded 2 (SIM2s), a basic helix-loop-helix/PAS (bHLH/PAS) transcription factor, is upregulated in pancreatic and prostate tumours; however, a mechanistic role for SIM2s in these cancers is unknown. Microarray studies in prostate DU145 cells identified the pro-cell death gene, BNIP3 (Bcl-2/adenovirus E1B 19 kDa interacting protein 3), as a novel putative target of SIM2s repression. Further validation showed BNIP3 repression in several prostate and pancreatic carcinoma-derived cell lines with ectopic expression of human SIM2s. BNIP3 levels are enhanced in prostate carcinoma cells upon short interfering (si)RNA-mediated knockdown of endogenous SIM2s. Chromatin immunoprecipitation and promoter studies show that SIM2s represses BNIP3 through its activities at the proximal promoter hypoxia response element (HRE), the site through which the bHLH/PAS family member, hypoxia-inducible factor 1a (HIF1a), induces BNIP3. SIM2s attenuates BNIP3 hypoxic induction via the HRE, and increased hypoxic induction of BNIP3 occurs with siRNA knockdown of endogenous SIM2s in prostate PC3AR þ cells. BNIP3 is implicated in hypoxia-induced cell death processes. Prolonged treatment of PC3AR þ cells with hypoxia mimetics, DP and DMOG, confers hypoxia-induced autophagy, measured by enhanced LC3-II levels and SQSTM1/p62 turnover. We show that PC3AR þ cells expressing ectopic SIM2s have enhanced survival in these conditions. Induction of LC3-II and turnover of SQSTM1/p62 are attenuated in PC3AR þ / SIM2s DMOG and hypoxia-treated cells, suggesting that SIM2s may attenuate autophagic cell death processes, perhaps through BNIP3 repression. These data show, for the first time, SIM2s cross-talk on an endogenous HRE. SIM2s' functional interference with HIF1a activities on BNIP3 may indicate a novel role for SIM2s in promoting tumourigenesis.

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Section: Identification Of Bnip3 As a Putative Target Of Repression Bmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

The HIF1α-inducible pro-cell death gene BNIP3 is a novel target of SIM2s repression through cross-talk on the hypoxia response element

Farrall

Whitelaw

2009

Oncogene

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“…Between the two datasets, there are a total of 113 tumor samples and 113 normal samples [15,16]. Normal samples are extracted from tissue adjacent to prostate tumors.…”

Section: Microarray Datamentioning

confidence: 99%

Combining multiple microarray studies using bootstrap meta-analysis

Barrett

Phan

Wang

2008

2008 30th Annual International Conference of the IEEE Engineering in Medicine and Biology Society

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Microarray technology has enabled us to simultaneously measure the expression of thousands of genes. Using this high-throughput technology, we can examine subtle genetic changes between biological samples and build predictive models for clinical applications. Although microarrays have dramatically increased the rate of data collection, sample size is still a major issue when selecting features. Previous methods show that combining multiple microarray datasets improves feature selection using simple methods such as fold change. We propose a wrapper-based gene selection technique that combines bootstrap estimated classification errors for individual genes across multiple datasets and reduces the contribution of datasets with high variance. We use the bootstrap because it is an unbiased estimator of classification error that is also effective for small sample data. Coupled with data combination across multiple datasets, we show that our metaanalytic approach improves the biological relevance of gene selection using prostate and renal cancer microarray data.

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“…Field cancerization is however evident at the genetic as well as the epigenetic level, as we have shown by altered telomeres in whole tissue TAHN extracts (11) and as shown by others by gene promoter methylation of APC, RARß2 and RASSF1A (34). Field cancerization in prostatic tissues is also evidenced by RNA/ protein expression analysis (35,36). In a similar study, but without validation by qRT-PCR, Chandran and colleagues reported differentially expressed transcripts when comparing tumor associated matched tissues to cancer-free controls utilizing an Affymetrix platform (35).…”

Section: Discussionmentioning

confidence: 84%

“…Field cancerization in prostatic tissues is also evidenced by RNA/ protein expression analysis (35,36). In a similar study, but without validation by qRT-PCR, Chandran and colleagues reported differentially expressed transcripts when comparing tumor associated matched tissues to cancer-free controls utilizing an Affymetrix platform (35). Of note, the authors claim that these transcripts would not be identified as differentially expressed when compared to tumors.…”

Section: Discussionmentioning

confidence: 95%

Differential gene expression in tumor adjacent histologically normal prostatic tissue indicates field cancerization

Haaland

Heaphy²,

Butler³

et al. 2009

Int J Oncol

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Abstract. Field cancerization denotes the occurrence of aberrant cells in tumor adjacent histologically normal tissues (TAHN). To characterize field cancerization in prostate cancer, we used RNA from paired patient tumor and TAHN tissues excised at 1 cm from the tumor margin and subjected them to microarray expression analysis comparative to RNA from normal cancer-free prostatic tissues. Eleven novel transcripts were significantly up-regulated in TAHN tissues and also in tumors. Expression of early growth response protein 1, tristetraprolin, testican, and fatty acid synthase, mutually up-regulated at different levels in tumors and TAHN tissues was confirmed by quantitative reverse transcriptase PCR in the experimental and in an independent validation set. This study offers proof of expressional changes in field cancerized prostatic TAHN tissues at defined distances from tumor margins. Markers of field cancerized prostatic tissues could be early diagnostic indicators in biopsies after abnormal prostate-specific antigen and digital rectal examination and independent of cancerous histology and/or early targets for chemo-preventive intervention in pre-malignant disease.

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Differences in gene expression in prostate cancer, normal appearing prostate tissue adjacent to cancer and prostate tissue from cancer free organ donors

Abstract: Background: Typical high throughput microarrays experiments compare gene expression across two specimen classes -an experimental class and baseline (or comparison) class.

Cited by 135 publications

References 31 publications

The HIF1α-inducible pro-cell death gene BNIP3 is a novel target of SIM2s repression through cross-talk on the hypoxia response element

The HIF1α-inducible pro-cell death gene BNIP3 is a novel target of SIM2s repression through cross-talk on the hypoxia response element

Combining multiple microarray studies using bootstrap meta-analysis

Differential gene expression in tumor adjacent histologically normal prostatic tissue indicates field cancerization

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