Immunohistochemical Expression of BRCA1 and Lethal Prostate Cancer

Fiorentino, Michelangelo; Judson, Gregory; Penney, Kathryn L.; Flavin, Richard; Stark, Jennifer R.; Fiore, Christopher; Fall, Katja; Martin, Neil E.; Ma, Jing; Sinnott, Jennifer A.; Giovannucci, Edward; Stampfer, Meir J.; Sesso, Howard D.; Kantoff, Philip W.; Finn, Stephen P.; Loda, Massimo; Mucci, Lorelei A.

doi:10.1158/0008-5472.can-09-4100

Cited by 33 publications

(32 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Areas of negative and positive staining were found in the same tumor, and PML bodies were rarely visualized. This lack of PML bodies in tumor cells can explain why prostate tumors exhibit high levels of expression of E2F target genes such as EZH2 (Stanbrough et al 2006) and BRCA1 (Schayek et al 2009;Fiorentino et al 2010). Interestingly, BRCA1 was one of the genes more efficiently down-regulated in PML-senescent fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

Regulation of E2Fs and senescence by PML nuclear bodies

Vernier¹,

Bourdeau²,

et al. 2011

View full text Add to dashboard Cite

The tumor suppressor PML (promyelocytic leukemia protein) regulates cellular senescence and terminal differentiation, two processes that implicate a permanent exit from the cell cycle. Here, we show that the mechanism by which PML induces a permanent cell cycle exit and activates p53 and senescence involves a recruitment of E2F transcription factors bound to their promoters and the retinoblastoma (Rb) proteins to PML nuclear bodies enriched in heterochromatin proteins and protein phosphatase 1a. Blocking the functions of the Rb protein family or adding back E2Fs to PML-expressing cells can rescue their defects in E2F-dependent gene expression and cell proliferation, inhibiting the senescent phenotype. In benign prostatic hyperplasia, a neoplastic disease that displays features of senescence, PML was found to be up-regulated and forming nuclear bodies. In contrast, PML bodies were rarely visualized in prostate cancers. The newly defined PML/Rb/E2F pathway may help to distinguish benign tumors from cancers, and suggest E2F target genes as potential targets to induce senescence in human tumors.

show abstract

Section: Discussionmentioning

confidence: 99%

Regulation of E2Fs and senescence by PML nuclear bodies

Vernier¹,

Bourdeau²,

et al. 2011

View full text Add to dashboard Cite

show abstract

“…However, whereas mutations in BRCA1 may influence familial prostate cancer progression, few studies have examined BRCA1 protein expression in prostate cancer tumor tissue. Fiorentino and colleagues (43) had addressed this important point and they found that human prostate tumor samples stained positive for BRCA1 had significantly higher Gleason score, PSA at diagnosis, and tumor proliferation as well as significantly worse prognosis than those with negative BRCA1 staining. Additionally, our results showing that BRCA1 loss of function is also involved in the differential response to DNA damage agents can also explain why the evolution of the disease could be favored or not by the presence of BRCA1 mutation.…”

Section: Discussionmentioning

confidence: 99%

BRCA1 Loss Induces GADD153-Mediated Doxorubicin Resistance in Prostate Cancer

Luca

Vázquez

Moiola

et al. 2011

Molecular Cancer Research

View full text Add to dashboard Cite

BRCA1 plays numerous roles in the regulation of genome integrity and chemoresistance. Although BRCA1 interaction with key proteins involved in DNA repair is well known, its role as a coregulator in the transcriptional response to DNA damage remains poorly understood. In this study, we show that BRCA1 plays a central role in the transcriptional response to genotoxic stress in prostate cancer. BRCA1 expression mediates apoptosis, cell-cycle arrest, and decreased viability in response to doxorubicin treatment. Xenograft studies using human prostate carcinoma PC3 cells show that BRCA1 depletion results in increased tumor growth. A focused survey of BRCA1-regulated genes in prostate carcinoma reveals that multiple regulators of genome stability and cell-cycle control, including BLM, FEN1, DDB2, H3F3B, BRCA2, CCNB2, MAD2L1, and GADD153, are direct transcriptional targets of BRCA1. Furthermore, we show that BRCA1 targets GADD153 promoter to increase its transcription in response to DNA damage. Finally, GADD153 depletion significantly abrogates BRCA1 influence on cell-cycle progression and cell death in response to doxorubicin treatment. These findings define a novel transcriptional pathway through which BRCA1 orchestrates cell fate decisions in response to genotoxic insults, and suggest that BRCA1 status should be considered for new chemotherapeutic treatment strategies in prostate cancer. Mol Cancer Res; 9(8); 1078-90. Ó2011 AACR.

show abstract

“…Lower levels of agreement were seen for ER-β categorical scores (; κ = 0.80-0.86), negative/positive and categorical scores for aromatase (κ=0.41-0.67) and HER2 (κ =0.53-0.72). Many other studies [51][52][53][54] also report using Lucia software for their study.…”

Section: Special Purpose Softwarementioning

confidence: 99%

Image Analysis Tools for Evaluation of Microscopic Views of Immunohistochemically Stained Specimen in Medical Research–a Review

2011

View full text Add to dashboard Cite

The aim of this study is to review the methods being used for image analysis of microscopic views of immunohistochemically stained specimen in medical research. The solutions available range from general purpose software to commercial packages. Many studies have developed their own custom written programs based on some general purpose software available. Many groups have reported development of computer aided image analysis programs aiming at obtaining faster, simpler and cheaper solutions. Image analysis tools namely Aperio, Lucia, Metaview, Metamorph, ImageJ, Scion, Adobe Photoshop, Image Pro Plus are also used for evaluation of expressions using immunohistochemical staining. An overview of such methods used for image analysis is provided in this paper. This study concludes that there is good scope for development of freely available software for staining intensity quantification, which a medical researcher could easily use without requiring high level computer skills.

show abstract

Immunohistochemical Expression of BRCA1 and Lethal Prostate Cancer

Cited by 33 publications

References 20 publications

Regulation of E2Fs and senescence by PML nuclear bodies

Regulation of E2Fs and senescence by PML nuclear bodies

BRCA1 Loss Induces GADD153-Mediated Doxorubicin Resistance in Prostate Cancer

Image Analysis Tools for Evaluation of Microscopic Views of Immunohistochemically Stained Specimen in Medical Research–a Review

Contact Info

Product

Resources

About