Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Expression data from MMTV-PDK1 transgenic mice

ABSTRACT: The role of PDK1 on mammary tumorigenesis and its interaction with PPARdelta, was assessed. Transgenic mice were generated in which PDK1 was expressed in the mammary epithelium. We used microarrays to analyse global gene expression changes in MMTV-PDK1 transgenic mice versus wild-type mice and determine any differential responses to GW501516 treatment. RNA was isolated (RNeasy Mini Kit, Qiagen) from mammary gland tissue from nulliparious transgenic and wild-type mice maintained on normal rodent chow or a diet supplemented with GW501516 for 1 week.

ORGANISM(S): Mus musculus

SUBMITTER: Robert Glazer

PROVIDER: E-GEOD-27083 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

PPARδ activation acts cooperatively with 3-phosphoinositide-dependent protein kinase-1 to enhance mammary tumorigenesis.

Pollock Claire B CB Yin Yuzhi Y Yuan Hongyan H Zeng Xiao X King Sruthi S Li Xin X Kopelovich Levy L Albanese Chris C Glazer Robert I RI

PloS one 20110113 1

Peroxisome proliferator-activated receptorδ (PPARδ) is a transcription factor that is associated with metabolic gene regulation and inflammation. It has been implicated in tumor promotion and in the regulation of 3-phosphoinositide-dependent kinase-1 (PDK1). PDK1 is a key regulator of the AGC protein kinase family, which includes the proto-oncogene AKT/PKB implicated in several malignancies, including breast cancer. To assess the role of PDK1 in mammary tumorigenesis and its interaction with PPA ...[more]

PMID: 21297860

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Project description:Dipyridamole (DPM) is widely used to prevent strokes and vascular thrombosis. Combination therapy of DPM and antimetabolites has shown synergistic anticancer activity. This study investigated the chemopreventive effects of DPM in the mouse mammary tumor virus promoter driven polyoma middle T oncoprotein (MMTV-PyMT) metastatic breast cancer model. We also investigated the effects of DPM on gene and miRNA expression. Chemopreventive activity was assessed by comparing the time to onset of palpable lesions, primary tumor growth kinetics and the number of lung metastases in transgenic mice treated with DPM or vehicle. Gene expression and microRNA (miRNA) expression profiles of mammary tumor tissues were then analyzed using the Affymetrix GeneChipM-BM-. or miRNA 2.0 arrays. Real-time quantitative PCR (qPCR) was used to confirm changes in gene expression. Treatment with DPM beginning at the age of four weeks delayed the onset of palpable lesions, delayed tumor progression and suppressed lung metastasis. Microarray gene expression analysis identified 253 genes differentially expressed between DPM-treated and control mammary tumors. miRNA expression analysis revealed that 53 miRNAs were altered by DPM treatment. The results indicate that DPM has chemoprevention activity against breast cancer tumorigenesis and metastasis in mice. The array analyses provide insights into potential mechanisms of DPMM-bM-^@M-^Ys chemopreventive effects, involving upregulation of several genes and miRNAs known to suppress cancer growth and/or metastasis and downregulation of genes known to promote cancer. Some of these genes have not been previously studied in breast cancer and may serve as novel molecular targets for breast cancer chemoprevention. MMTV-PyMT+ female mice were randomly divided into a DPM treatment group (n=10 mice, total of 100 glands) and a vehicle (control) group (n=7 mice, total of 70 glands). When mice were four weeks old, when hyperplasia lesions begin to develop in the FVB strain (21), DPM (10 mg/kg) or vehicle was injected IP into the peritoneum of each mouse on a 5 days on/2 days off dosing schedule for a total of 11 weeks (week one=injection one), until mice were 15 weeks of age. Each of the 10 mammary tumors per mouse was monitored until the study end point. A total six breast tumor RNA samples were used for microarray analysis, with three form mice treated with DPM and three from mice treated with vehicle.

Dataset Information

Expression data from MMTV-PDK1 transgenic mice

Publications

PPARδ activation acts cooperatively with 3-phosphoinositide-dependent protein kinase-1 to enhance mammary tumorigenesis.

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