Article

High expression of ubiquitin carboxy-terminal hydrolase-L1 and -L3 mRNA predicts early recurrence in patients with invasive breast cancer.

Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
Cancer Science (impact factor: 3.33). 06/2006; 97(6):523-9. DOI:10.1111/j.1349-7006.2006.00202.x pp.523-9
Source: PubMed

ABSTRACT The present study investigated the mRNA expression level of ubiquitin c-terminal hydrolase (UCH)-L1 and -L3 in breast cancer tissue and aimed to elucidate its association with tumor characteristics and patient prognosis. UCH-L1 and UCH-L3 mRNA levels in invasive breast cancer (n = 100) were determined by a real-time polymerase chain reaction (PCR) assay and their relationship with various clinicopathological characteristics of breast tumors as well as patient prognosis were studied. UCH-L3 mRNA level was significantly upregulated in breast cancer tissue compared to adjacent normal breast tissue (P < 0.005), and UHC-L1 mRNA level also showed a non-significant increase in tumor tissue compared to adjacent normal breast tissue. Both UCH-L1 and UCH-L3 mRNA levels were significantly higher in high histological grade tumors than in low histological grade tumors (P < 0.001 and P < 0.005, respectively). High UCH-L1 mRNA level was significantly associated with negative estrogen receptor status (P < 0.05) and negative progesterone receptor status (P < 0.05). Patients with both UCH-L1 and UCH-L3 mRNA high tumors showed a significantly poorer prognosis than those in the UCH-L1 or UCH-L3 mRNA low group (P < 0.005). These observations that UCH-L3 mRNA level is upregulated in breast cancer tissue, and breast tumors with both UCH-L1 and UCH-L3 mRNA high expression are associated with a poor prognosis, suggest the possible involvement of UCH-L1 and UCH-L3 in the pathogenesis and progression of breast cancer.

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    Article: Expression and functional studies of ubiquitin C-terminal hydrolase L1 regulated genes.
    Anjali Bheda, Julia Shackelford, Joseph S Pagano
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    ABSTRACT: Deubiquitinating enzymes (DUBs) have been increasingly implicated in regulation of cellular processes, but a functional role for Ubiquitin C-terminal Hydrolases (UCHs), which has been largely relegated to processing of small ubiquitinated peptides, remains unexplored. One member of the UCH family, UCH L1, is expressed in a number of malignancies suggesting that this DUB might be involved in oncogenic processes, and increased expression and activity of UCH L1 have been detected in EBV-immortalized cell lines. Here we present an analysis of genes regulated by UCH L1 shown by microarray profiles obtained from cells in which expression of the gene was inhibited by RNAi. Microarray data were verified with subsequent real-time PCR analysis. We found that inhibition of UCH L1 activates genes that control apoptosis, cell cycle arrest and at the same time suppresses expression of genes involved in proliferation and migration pathways. These findings are complemented by biological assays for apoptosis, cell cycle progression and migration that support the data obtained from microarray analysis, and suggest that the multi-functional molecule UCH L1 plays a role in regulating principal pathways involved in oncogenesis.
    PLoS ONE 02/2009; 4(8):e6764. · 4.09 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

adjacent normal breast tissue
 
breast cancer
 
breast cancer tissue
 
histological grade tumors
 
invasive breast cancer
 
low histological grade tumors
 
mRNA expression level
 
patient prognosis
 
poor prognosis
 
poorer prognosis
 
real-time polymerase chain reaction
 
tumor tissue
 
ubiquitin c-terminal hydrolase
 
UCH-L1 mRNA level
 
UCH-L3 mRNA
 
UCH-L3 mRNA level
 
UCH-L3 mRNA levels
 
UCH-L3 mRNA low group
 
UHC-L1 mRNA level
 
various clinicopathological characteristics