STANDARD_NAME	LANDIS_BREAST_CANCER_PROGRESSION_UP
SYSTEMATIC_NAME	M6875
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/LANDIS_BREAST_CANCER_PROGRESSION_UP
NAMESPACE	AFFY_MG_U74
DESCRIPTION_BRIEF	Genes up-regulated in preneoplastic mammary tissues and whose expression is maintained in tumors.
DESCRIPTION_FULL	Epidemiological studies indicate that parity enhances HER2/ErbB2/Neu-induced breast tumorigenesis. Furthermore, recent studies using multiparous, ErbB2/Neu-overexpressing mouse mammary tumor virus (MMTV-Neu) mice have shown that parity induces a population of cells that are targeted for ErbB2/Neu-induced transformation. Although parity accelerates mammary tumorigenesis, the pattern of tumor development in multiparous MMTV-Neu mice remains stochastic, suggesting that additional events are required for ErbB2/Neu to cause mammary tumors. Whether such events are genetic in nature or reflective of the dynamic hormonal control of the gland that occurs with pregnancy remains unclear. We postulated that young age at pregnancy initiation or chronic trophic maintenance of mammary epithelial cells might provide a cellular environment that significantly increases susceptibility to ErbB2/Neu-induced tumorigenesis. MMTV-Neu mice that were maintained pregnant or lactating beginning at 3 weeks of age demonstrated accelerated tumorigenesis, but this process was still stochastic, indicating that early pregnancy does not provide the requisite events of tumorigenesis. However, bitransgenic mice that were generated by breeding MMTV-Neu mice with a luteinizing hormone-overexpressing mouse model of ovarian hyperstimulation developed multifocal mammary tumors in an accelerated, synchronous manner compared to virgin MMTV-Neu animals. This synchrony of tumor development in the bitransgenic mice suggests that trophic maintenance of the mammary gland provides the additional events required for tumor formation and maintains the population of cells that are targeted by ErbB2/Neu for transformation. Both the synchrony of tumor appearance and the ability to characterize a window of commitment by ovariectomy/palpation studies permitted microarray analysis to evaluate changes in gene expression over a defined timeline that spans the progression from normal to preneoplastic mammary tissue. These approaches led to identification of several candidate genes whose expression changes in the mammary gland with commitment to ErbB2/Neu-induced tumorigenesis, suggesting that they may either be regulated by ErbB2/Neu and/or contribute to tumor formation.
PMID	16434967
GEOID	GSE3501
AUTHORS	Landis MD,Seachrist DD,Abdul-Karim FW,Keri RA
CONTRIBUTOR	Lauren Kazmierski
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 1S
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	100024_at,102197_at,102198_at,102243_at,102381_at,103059_at,103330_at,103423_at,103443_at,103794_i_at,103892_r_at,104480_at,160109_at,160112_at,160202_at,160249_at,160343_at,160546_at,160564_at,160688_at,160801_at,160977_at,92275_at,92440_at,92564_at,93013_at,93753_at,93842_at,94493_at,94821_at,95478_at,95518_at,95708_at,95746_at,96518_at,96627_at,97206_at,97335_at,97413_at,98593_at,98915_at,99011_at,99034_at,99452_at,99561_f_at,99584_at,99964_at
GENE_SYMBOLS	SHROOM3,NUCB2,KCNN4,EHF,ACSL4,FXYD3,STRBP,CYB561,CRYBG1,HAVCR1,ELL2,DSG2,SOX4,CHMP2B,ATP6AP2,TPD52,SRP19,ALDOC,LCN2,GOLPH3,SLC66A2,ARHGEF5,TFAP2C,IRF6,LRRFIP1,ID2,LITAF,DAP,CLDN3,XBP1,SS18L2,RETREG1,SERP1,ATP6V1A,WWC1,EBP,SPINT1,HAVCR1,PLET1,CMAS,RNF149,GALNT3,IRX3,LSR,CLDN7,CD82,VDR
FOUNDER_NAMES