<i>RAD21</i> and <i>KIAA0196</i> at 8q24 are amplified and overexpressed in prostate cancer

Porkka, Kati P.; Tammela, Teuvo L.J.; Vessella, Robert L.; Visakorpi, Tapio

doi:10.1002/gcc.10289

Cited by 70 publications

(54 citation statements)

References 24 publications

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“…The labeling of the cDNAs and the hybridizations were done as described previously in more detail. 13 Briefly, for each hybridization, labeled first-strand cDNAs were generated from 40 mg of total control (Cy3) and 5-azadC-and/or TSA-treated (Cy5) RNAs using oligo d(T) 15 primer and SuperScript II Reverse Transcriptase (Invitrogen). The labeled probes were then combined, purified and concentrated using Microcon YM-30 columns (Millipore, Billerica, MA).…”

Section: Cdna Microarray Expression Analysismentioning

confidence: 99%

Dual‐specificity phosphatase 1 and serum/glucocorticoid‐regulated kinase are downregulated in prostate cancer

Rauhala

Porkka

Tolonen

et al. 2005

Intl Journal of Cancer

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Inactivation of tumor suppressor genes through deletion, mutation and epigenetic silencing has been shown to occur in cancer. In our study, we combined DNA demethylation and histone deacetylation inhibition treatments with suppression subtraction hybridization (SSH) and cDNA microarrays to identify potentially epigenetically downregulated genes in PC-3 prostate cancer cell line. We found 11 genes whose expression was upregulated after relieving epigenetic regulation. Expression of 3 genes [dual-specificity phosphatase 1 (DUSP1), serum/glucocorticoid regulated kinase (SGK) and spermidine/spermine N1-acetyltransferase (SAT)] was subsequently studied in clinical sample material using real-time quantitative RT-PCR and immunohistochemistry. The DUSP1 and SGK mRNA expression was lower in hormone-refractory prostate carcinomas compared to benign prostate hyperplasia (BPH) or untreated prostate carcinomas. BPH, normal prostate and highgrade prostate intraepithelial neoplasia (PIN) expressed high levels of DUSP1 and SGK proteins. Ninety-two percent and 48% of the prostate carcinomas showed almost complete lack of DUSP1 and SGK proteins, respectively, indicating common downregulation of these genes. The genomic bisulphite sequencing did not reveal dense hypermethylation in the promoter regions of either DUSP1 or SGK. In conclusion, the data suggest that downregulation of DUSP1 and SGK is an early event and could be important in the tumorigenesis of prostate cancer. ' 2005 Wiley-Liss, Inc.

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Section: Cdna Microarray Expression Analysismentioning

confidence: 99%

Dual‐specificity phosphatase 1 and serum/glucocorticoid‐regulated kinase are downregulated in prostate cancer

Rauhala

Porkka

Tolonen

et al. 2005

Intl Journal of Cancer

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“…These two markers have been found to be deregulated in different types of tumors, including endometrioid, prostate, breast and oral squamous carcinoma together with acute lymphoblastic leukemia (8,9,11,12,14,(18)(19)(20)(21)(22)(23)(24)(25). The present study was designed to address the hypothesis of cohesin deregulation in endometrial cancer.…”

Section: Introductionmentioning

confidence: 97%

“…These features include genomic instability, impaired DNA repair and anomalies concerning gene expression (4)(5)(6)(7). The deregulation of cohesin expression and cohesin-regulated genes is common in numerous types of human cancer (8)(9)(10)(11)(12)(13), including endometrial cancer (14). Furthermore, cohesin-defective cells have been discovered to be sensitive to ionizing radiation and DNA-damaging drugs (8,15).…”

Section: Introductionmentioning

confidence: 99%

Deregulation of RAD21 and RUNX1 expression in endometrial cancer

et al. 2012

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Abstract. Cohesins and cohesin-regulated genes are deregulated in numerous types of human cancer. However, data concerning their status and role in endometrial cancer are scarce. This study aimed to determine the clinical significance of double-strand-break repair protein rad21 homolog (RAD21) and runt-related transcription factor 1 (RUNX1) gene dosage and mRNA expression in endometrial cancer. RAD21 is a component of the cohesin complex, crucial for chromosome segregation and DNA repair. RUNX1 is the transcription factor implicated in RAD21 regulation. The study group included 144 endometrial cancer patients. RAD21 and RUNX1 expression profiles were measured by reverse-transcription quantitative PCR. RAD21 gene dosage was determined by quantitative PCR. RAD21 gene dosage was associated with RAD21 mRNA expression (ρ=0.22; p=0.009). Furthermore, RAD21 expression strongly correlated with RUNX1 expression (ρ=0.43; p<0.0000001). Increased RAD21 gene dosage correlated with more advanced tumor stage (p=0.021), higher grade (p= 0.021), cervical involvement (p= 0.01) and the absence of obesity (p=0.025), while RAD21 mRNA expression correlatd with cervical involvement (p=0.027). The mRNA expression of RAD21 and RUNX1 was found to be deregulated and co-dependent in endometrial cancer. RAD21 gene dosage is associated with unfavorable tumor characteristics. However, elucidating the role of these molecular markers in endometrial oncogenesis requires further investigation, including functional studies and survival analysis.

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“…7,8 Whether there is amplification of MYC in the likely precursor to many prostate adenocarcinomas, high-grade prostatic intraepithelial neoplasia (HGPIN), is controversial because MYC amplification has been reported in up to 50% of HGPIN lesions, 9 but more recent experiments revealed a lack of MYC amplification in HGPIN. 10 Other genes, such as TRPS1, EIF3S3, RAD21, KIAA0916, and PSCA are within or near the 8q24 region and, at times, are also amplified in prostate carcinoma [11][12][13][14][15] complicating the data implicating MYC as the key target of amplification in this chromosomal region.…”

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confidence: 99%

Nuclear MYC protein overexpression is an early alteration in human prostate carcinogenesis

et al. 2008

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The MYC onco-protein is a transcription factor that regulates cell proliferation, metabolism, protein synthesis, mitochondrial function and stem cell renewal. A region on chromosome 8q24 encompassing the MYC locus is amplified in prostate cancer, but this occurs mostly in advanced disease suggesting that MYC alterations occur late in prostate cancer. In contrast, MYC mRNA is elevated in most prostate cancers, even those of relatively low stage and grade (eg Gleason score 6) suggesting that MYC plays a role in initiation. However, since MYC protein levels are tightly regulated, elevated MYC mRNA does not necessarily imply elevated MYC protein. Thus, it is critical to determine whether MYC protein is elevated in human prostate cancer, and if so, at what stage of the disease this elevation occurs. Prior studies of MYC protein localization have been hampered by lack of suitable antibodies and controls. We utilized a new anti-MYC antibody coupled with genetically defined control experiments to localize MYC protein within human tissue microarrays consisting of normal, atrophy, PIN, primary adenocarcinoma, and metastatic adenocarcinoma. Nuclear overexpression of MYC protein occurred frequently in luminal cells of PIN, as well as in most primary carcinomas and metastatic disease. MYC protein did not correlate with gain of 8q24, suggesting alternative mechanisms for MYC overexpression. These results provide evidence that upregulation of nuclear MYC protein expression is a highly prevalent and early change in prostate cancer and suggest that increased nuclear MYC may be a critical oncogenic event driving human prostate cancer initiation and progression.

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RAD21 and KIAA0196 at 8q24 are amplified and overexpressed in prostate cancer

Cited by 70 publications

References 24 publications

Dual‐specificity phosphatase 1 and serum/glucocorticoid‐regulated kinase are downregulated in prostate cancer

Dual‐specificity phosphatase 1 and serum/glucocorticoid‐regulated kinase are downregulated in prostate cancer

Deregulation of RAD21 and RUNX1 expression in endometrial cancer

Nuclear MYC protein overexpression is an early alteration in human prostate carcinogenesis

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