Chemoprevention of Prostate Cancer Initiation in a Novel Transgenic Mouse Model by Targeting 15-Lipoxygenase-1

FLiMP mice, which conditionally express prostatic human 15-LO-1, display mouse prostatic intraepithelial neoplasia (mPIN) by week 20, but do not progress to cancer when on normal diet. To examine for the up-regulated and downregulated genes in the prostates of FLiMP we used pooled cDNA sets of indiv...

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Bibliographic Details
Main Author: Kelavkar, Uddhav P
Format: Report
Language:English
Subjects:
ANATOMICAL MODELS
CANCER
CHEMOTHERAPY
COMPUTATIONS
CYCLOOXYGENASE
DIET
FILTERS
GENES
HYBRIDIZATION
INTENSITY
MARKERS
Medicine and Medical Research
NEOPLASMS
ONCOGENESIS
PROSTATE CANCER
PROSTATE GLAND
PUFAS(POLYUNSATURATED FATTY ACIDES)
REGIONS
SCANNING
STARTING
SUCROSE
SWITCHES
TRANSCRIPTION(GENETICS)
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Summary:FLiMP mice, which conditionally express prostatic human 15-LO-1, display mouse prostatic intraepithelial neoplasia (mPIN) by week 20, but do not progress to cancer when on normal diet. To examine for the up-regulated and downregulated genes in the prostates of FLiMP we used pooled cDNA sets of individual prostate regions from FLiMP+/- and FLiMP+/+ mice and age matched nontransgenic C57BL/6 littermates were used for cDNA production. Hybridization was performed on pretreated 38.5K mouse Illumina MEEBO oligonucleotide (25,000 genes) microarray slides. The slides were scanned and intensity data were further analyzed with GeneSpring 7.0 software and normalized. All of the data were filtered very heavily yielding a total of 7037 genes. This list was used as the starting list for fold-change calculations (p 0.001, fold change 2). Fold change calculations were performed and genes were pooled and uploaded into the PANTHER gene expression analysis tool (http://panther.appliedbiosystems.com) to examine for pathways. The levels of Phospholipase C-gamma 2 (PLC- 2) mRNA increased with age and were 8 times higher at week 32 and that a similar pattern in the levels of Phosphatase and tensin homolog (PTEN) and SMARCA3 related Switch/Sucrose non-fermentable (SWI/SNF) mRNA decreased with age, both of which were 4 times lower at week 32 in all prostate lobes of the FLiMP mice. Consequence of such differences in the expression levels of these genes that have wide roles in the process of prostate carcinogenesis in relation to the susceptibility of mouse prostate glands to PIN via 15-LO-1 expression is currently unknown. We will exploit the utility of these markers to examine the n-6 and n-3 fatty acids effects on PIN development. The original document contains color images.