Prognostic value of PAI1 in invasive breast cancer: evidence that tumor-specific factors are more important than genetic variation in regulating PAI1 expression.

Prognostic value of PAI1 in invasive breast cancer: evidence that tumor-specific factors are more important than genetic variation in regulating PAI1 expression. Research Abstract Details 

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Prognostic value of PAI1 in invasive breast cancer: evidence that tumor-specific factors are more important than genetic variation in regulating PAI1 expression. Abstract Text:

Mark D Sternlicht,Alison M Dunning,Dan H Moore,Paul D P Pharoah,David G Ginzinger,Koei Chin,Joe W Gray,Frederic M Waldman,Bruce A J Ponder,Zena Werb,

Plasminogen activator inhibitor-1 (PAI1) can promote cancer progression, and its protein expression in tumors is an independent indicator of poor prognosis in many forms of cancer. Here, we show that high PAI1 mRNA levels also predict for shorter overall survival in two independent breast cancer data sets, highlighting the importance of its transcriptional regulation. The -675insG (4G/5G) single-nucleotide polymorphism in the PAI1 gene promoter has been shown to influence PAI1 transcription, with the 4G allele eliciting higher reporter gene expression in vitro and higher levels of circulating PAI1 in vivo. Nevertheless, its genotypic distribution in 2,539 British women with invasive breast cancer was virtually identical to that seen in 1,832 matched controls (P = 0.72), and annual mortality rates for 4G4G, 4G5G, and 5G5G cases were 2.6%, 2.8%, and 3.1% per year, respectively (P = 0.10). Thus, there was no association with breast cancer incidence or outcome, and in a separate set of breast cancers, the 4G/5G single-nucleotide polymorphism showed no association with PAI1 mRNA expression (P = 0.85). By contrast, connective tissue growth factor (CTGF), which can regulate PAI1 expression in culture, was associated with PAI1 expression in three independent cohorts (P << 0.0001). In addition, PAI1 gene copy number differences in the tumors were correlated with PAI1 mRNA expression (P = 0.0005) and seemed to affect expression independently of CTGF. Thus, local factors, such as CTGF and genomic amplification, seem to be more important than germ line genetic variation in influencing PAI1 expression and its untoward effects in breast cancer.

Prognostic value of PAI1 in invasive breast cancer: evidence that tumor-specific factors are more important than genetic variation in regulating PAI1 expression. Publishing Authors By Initials

MD Sternlicht,AM Dunning,DH Moore,PD Pharoah,DG Ginzinger,K Chin,JW Gray,FM Waldman,BA Ponder,Z Werb,

For similar genetic phenomena: variation (genetics) research abstracts see: genetic phenomena: variation (genetics) research

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Prognostic value of PAI1 in invasive breast cancer: evidence that tumor-specific factors are more important than genetic variation in regulating PAI1 expression. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Cancer epidemiology, biomarkers & prevention : a p

VOLUME: 15

Page Numbers: 2107-14

Journal Abbreviation: Cancer Epidemiol. Biomarkers P

ISSN: 1055-9965

DAY: 3

MONTH: Nov

YEAR: 2006

Prognostic value of PAI1 in invasive breast cancer: evidence that tumor-specific factors are more important than genetic variation in regulating PAI1 expression. Information

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LANGUAGE: eng

NlmUniqueID: 9200608

Prognostic value of PAI1 in invasive breast cancer: evidence that tumor-specific factors are more important than genetic variation in regulating PAI1 expression. Keywords Mesh Terms:

KEYWORDS: Variation (Genetics)

MESH TERMS: metabolism

Chemical & Substance for Abstract: Prognostic value of PAI1 in invasive breast cancer: evidence that tumor-specific factors are more important than genetic variation in regulating PAI1 expression. Information

Substance Name: connective tissue growth factor

Registry Number: 139568-91-5

Grant and Affiliation Information for Prognostic value of PAI1 in invasive breast cancer: evidence that tumor-specific factors are more important than genetic variation in regulating PAI1 expression.

AFFILIATION: Department of Anatomy, University of California San Francisco, 513 Parnassus Avenue, HSW-1301 San Francisco, CA 94143-0452, USA. mark.sternlicht@ucsf.edu

Country: United States

AGENCY: United States NCI

GRANT: CA72006

ACRONYM: CA

MEDLINETA: Cancer Epidemiol Biomarkers Pr

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