M N Gould

..These results identify a calcium-dependent NF-kappaB pathway as a molecular target of perillyl alcohol activity in different cancer cell types...

..Animal studies and protein modeling suggest that the Ile655Val polymorphism located in the transmembrane domain of the HER2 protein might influence breast cancer development by altering the efficiency of homodimerization...

..The cyclooxygenase-2 inhibitor celecoxib (Celebrex) is a nonsteroidal anti-inflammatory drug and as such is a potential candidate for the prevention of hormonally nonresponsive breast cancer...

..We investigated whether the systemic inflammation induced by Freund's adjuvant (FA) promotes mammary carcinogenesis in a rat model in which cancer is induced by the neu oncogene...

..Here we describe mechanisms through which Mcs5a may reduce mammary carcinoma susceptibility...

..These and related findings have the potential to yield advancements both in translation-prevention research and in basic molecular genetics...

..e. equal total energies deposited), survival is not statistically different for the two treatments over a wide range of doses. Thus, imparting equal energies to smaller intranuclear volumes does not appear to modulate cell killing...

..This allele-specific differential expression is environmentally controlled...

..Lymphomas and thymic tumours were negative for NGAL immuno-labeling. Knowledge about the location of NGAL in normal cells and in disease states provides the first clues towards understanding its biological function...

..Together, these data suggest that one or more breast cancer-related genes are located within the dominantly acting WKy allele at the Mcs7 locus...

..In addition, we identified an interaction between Mcs8 and a region on chromosome 6 termed Mcsm1 (modifier of Mcs), which had no significant main effect on mammary cancer susceptibility in this genetic analysis...

..We illustrate these methods on allelic-loss data from induced rat mammary tumours and human bladder cancers...

..The isolation of the Mcs genes may help elucidate novel mechanisms of carcinogenesis, provide information important for human breast cancer risk estimation, and also provide unique drug discovery targets for breast cancer prevention...

..The realized benefits in this case do not outweigh the price paid for loss of individual specific information. Pooling is beneficial when many subjects are pooled, provided that independent samples contribute to multiple pools...

..The methodology is used in a study of mammary cancer in the rat, where four distinct patterns of expression are possible...

..Together, these points demonstrate the unique utility of this new gene expression screen to identify altered gene expression in a complex in vivo environment...

..The establishment of the rat Brca2 knockout model provides a means to study the role of Brca2 in increasing cancer susceptibility and inducing a novel ocular phenotype not previously associated with this gene...

..Resulting tumors resemble a clinical phenotype of ER+/PR-, and when combined with a heterozygous p53 genotype, ER-/PR-...

..To resolve the assignment and to localize the Cp gene on the rat genetic linkage map, we used linkage analysis to confirm that rat Cp lies on chromosome 2...

..The minor allele of rs6476643 increases risk, whereas the rs2182317 minor allele decreases risk. Both alleles have a high population frequency and a low penetrance toward breast cancer risk...

..NGAL levels were stratified as high or low in breast cancers from a cohort of node-positive patients with known outcome. No significant association between NGAL expression and disease-free or overall survival was observed...

..0, 7.5, and 4.5 Mb of rat chromosome 5, and the orthologous regions are on human chromosome 9 and mouse chromosome 4. These loci will provide unbiased candidate gene loci for evaluation in human case-control association studies...

..Long-term grafts of Min/+ mammary glands also gave rise to focal alveolar hyperplasias, indicating that the presence of the Min mutation also has a role in the development of these lesions...

..Based on results presented here, the Mcs5 locus has been physically located within a congenic interval on rat chromosome 5 between markers D5Uwm8 and D5Rat26...

..The identification of these independent loci within the Mcs1 COP allele provide a model of the genetic complexity of cancer...

..Using fluorescence in situ hybridization, we have localized Stat5a to rat chromosome band 10q32.1 and Yy1 to rat chromosome band 6q32...

..In contrast, prevention of mammary cancer by polycyclic hydrocarbons such as 7,12-dimethylbenz[a]anthracene occur by the induction of detoxifying phase II hepatic enzymes...

..In this review, we describe the efforts to generate genetically engineered rat models for breast cancer...

..The model is useful for assessing the efficacy of chemopreventive agents, specifically those compounds that target hormonally nonresponsive tumors...

..Our results suggest crosstalk between the Neu proto-oncogene and AR signaling pathways in the growth of both the normal and cancerous mammary epithelium...

..Our prevention model represents a cost-efficient in vivo system to determine whether the preventive effects of a compound extend to hormonally nonresponsive mammary lesions, for which new chemoprevention approaches are needed...

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..These findings highlight the potential of Ras to function as a modifier gene in repressing mammary carcinogenesis...

..In addition, these in vivo mammary studies for the first time identify domains in the mostly homologous region of Ras (amino acids 1-169) that strongly influence the oncogenic potency/specificity of H-Ras...

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..Finally, the data to be generated may provide clinical markers of breast cancer risk and novel targets for chemoprevention. ..

..This model will also provide functional information underlying genetic/environmental risk that could lead to strategies for risk reduction to this disease. ..

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..Finally, the data to be generated may provide clinical markers of breast cancer risk and novel targets for chemoprevention. ..

..It is also possible that it will provide risk markers for human breast cancer. Broadly, it will also likely provide new insights for interpretation of the results of genome-wide association studies for common diseases. ..

..This model will also provide functional information underlying genetic/environmental risk that could lead to strategies for risk reduction to this disease. ..

..It is also possible that it will provide risk markers for human breast cancer. Broadly, it will also likely provide new insights for interpretation of the results of genome-wide association studies for common diseases. ..

..Knowledge of these genes and their function will provide unique insights into the etiology of breast cancer. ..

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..cDNAs of candidate genes will then be cloned and characterized. Characterization will include an initial assay. Positive sequence will then be tested in vivo for MCS activity screen using a cell culture/in vitro using a transgenic model...

..The accomplishment of our goal may provide: additional insight and reagents to better estimate the genetic risk of women for breast cancer; and new targets for the development of drugs to prevent breast cancer. ..

..Such a gene also may serve as a target for the development of chemoprevention agents. ..

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..In addition, the identification of enhancer or suppressor gene products may lead to the development of new strategies in the prevention and treatment of this disease...