Novel Role for RGS1 in Melanoma Progression
Auerback Melanoma Research Laboratory, Cutaneous Oncology Program, UCSF Comprehensive Cancer Center, Department of Dermatology, University of California San Francisco, San Francisco, CA 94115, USA. The American journal of surgical pathology
(Impact Factor: 5.15).
06/2008; 32(8):1207-12. DOI: 10.1097/PAS.0b013e31816fd53c
RGS1 (regulator of G protein signaling 1) encodes a member of the regulator of G protein family. Recently, RGS1 was found to be overexpressed in gene expression-profiling studies of melanoma. However, no analyses have been reported of its expression at the protein level in melanoma. In this study, the potential impact of RGS1 as a molecular prognostic marker for melanoma was assessed using immunohistochemical analysis of a melanoma tissue microarray containing primary cutaneous melanomas from 301 patients. High RGS1 expression was significantly correlated with increased tumor thickness (P=0.0083), mitotic rate (P=0.04), and presence of vascular involvement (P<0.02). Kaplan-Meier analysis demonstrated a significant association between increasing RGS1 expression and reduced relapse-free survival (P=0.0032) as well as disease-specific survival (DSS) (P=0.018) survival. Logistic regression analysis showed RGS1 overexpression to be significantly correlated to sentinel lymph node metastasis (P=0.04). Multivariate Cox regression analysis showed that increasing RGS1 immunostaining had an independent impact on the relapse-free survival (P=0.0069) and DSS (P=0.0077) of this melanoma cohort. In the analysis of DSS, RGS1 expression level was the most powerful factor predicting DSS. RGS1 immunostaining retained independent prognostic impact even when sentinel lymph node status was included in the prognostic model (P=0.0039). These results validate the role of RGS1 as a novel prognostic marker for melanoma given its impact on the survival associated with melanoma.
Available from: Augusto Rendon
- "Single-nucleotide polymorphisms in this gene have been associated with spondylarteritis, type 1 diabetes mellitus and celiac disease –. In addition they are an independent prognostic marker of disease survival in melanomas . So far, there is no clear association with atherogenesis or CVD. "
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ABSTRACT: The burden of cardiovascular disease (CVD) cannot be fully addressed by therapy targeting known pathophysiological pathways. Even with stringent control of all risk factors CVD events are only diminished by half. A number of additional pathways probably play a role in the development of CVD and might serve as novel therapeutic targets. Genome wide expression studies represent a powerful tool to identify such novel pathways. We compared the expression profiles in monocytes from twenty two young male patients with premature familial CAD with those from controls matched for age, sex and smoking status, without a family history of CVD. Since all patients were on statins and aspirin treatment, potentially affecting the expression of genes in monocytes, twelve controls were subsequently treated with simvastatin and aspirin for 6 and 2 weeks, respectively.
By whole genome expression arrays six genes were identified to have differential expression in the monocytes of patients versus controls; ABCA1, ABCG1 and RGS1 were downregulated in patients, whereas ADRB2, FOLR3 and GSTM1 were upregulated. Differential expression of all genes, apart from GSTM1, was confirmed by qPCR. Aspirin and statins altered gene expression of ABCG1 and ADBR2. All finding were validated in a second group of twenty four patients and controls. Differential expression of ABCA1, RSG1 and ADBR2 was replicated. In conclusion, we identified these 3 genes to be expressed differently in CAD cases which might play a role in the pathogenesis of atherosclerotic vascular disease.
Available from: Gerald Pierard
- "As each probe has a unique length due to the stuffer sequence, electrophoresis conveniently separates and quantifies the amount of PCR product indicating the DNA copy number . Mutation-specific MLPA combines copy number detection and hot-spot mutations in a single assessment . "
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ABSTRACT: At present, immunohistochemistry is taken for granted in the establishment of malignant melanoma (MM) diagnosis. In recent years, molecular diagnosis in dermatopathology has benefited from a vast array of advances in the fields of genomics and proteomics. Sensitive techniques are available for detecting specific DNA and RNA sequences by molecular hybridization. This paper intends to update methods of molecular cytogenetics available as diagnostic adjuncts in the field of MM. Cytogenetics has highlighted the pathogenesis of atypical melanocytic neoplasms with emphasis on the activation of the mitogen-activated protein kinase (MAPK) signalling pathway during the initiation step of the neoplasms. 20 to 40% of MM families have mutations in the tumour suppressor gene p16 or CDKN2A. In addition, somatic mutations in p16, p53, BRAF, and cKIT are present in MM. Genome-wide scan analyses on MM indicate positive associations for genes involved in melanocytic naevi, but MM is likely caused by a variety of common low-penetrance genes. Molecular dermatopathology is expanding, and its use in the assessment of melanocytic neoplasms appears to be promising in the fields of research and diagnosis. Molecular dermatopathology will probably make its way to an increased number of diagnostic laboratories. The expected benefit should improve the patient management. This evolution points to a need for evolution in the training requirements and role of dermatopathologists.
Available from: Jillian Hurst
- "Family A/RZ RGS17/RGSZ2 " in prostate cancer ; " in lung cancer  RGS19/GAIP " in ovarian cancer ; regulates wnt/b-catenin signaling ; binding partner GIPC down-regulated in primary kidney tumors, colorectal tumors, gastric cancer, and prostate cancer  RGS20/RGSZ1 " in melanoma  Family B/R4 RGS1 " in melanoma ; " in head and neck squamous cell carcinoma ; " in adult T-cell leukemia ; " in renal cell carcinoma ; " in ovarian cancer ; " in cervical cancer ; " in mantle cell lymphoma  RGS2 # in ovarian cancer ; " in breast cancer ; " in fibrolamellar carcinoma ; # in prostate cancer ; # in acute myeloid leukemia ; " in mantle cell lymphoma  RGS3 " in docetaxel resistant breast cancers ; " associated with enhanced glioma cell motility ; " in soft tissue sarcomas  RGS4 " associated with enhanced glioma cell motility ; " in thyroid carcinoma ; # in ovarian cancer  RGS5 " in hepatocellular carcinoma ; " in breast cancer, melanoma, multiple myeloma, ovarian cancer, and acute myeloid leukemia ; " in fibrolamellar carcinoma  RGS8 N/A RGS13 # in mantle cell lymphoma ; " in B-and T-cell lymphoma  RGS16 " in pediatric high hyperdiploid acute lymphoblastic leukemias ; " in pineal parenchymal tumors ; p53 target gene in colorectal cancer  RGS18 N/A "
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ABSTRACT: The regulator of G-protein signaling (RGS) family is a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). In recent years, GPCRs have been linked to the initiation and progression of multiple cancers; thus, regulators of GPCR signaling are also likely to be important to the pathophysiology of cancer. This review highlights recent studies detailing changes in RGS transcript expression during oncogenesis, single nucleotide polymorphisms in RGS proteins linked to lung and bladder cancers, and specific roles for RGS proteins in multiple cancer types.
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