Rrp1b, a new candidate susceptibility gene for breast cancer progression and metastasis.
A novel candidate metastasis modifier, ribosomal RNA processing 1 homolog B (Rrp1b), was identified through two independent approaches. First, yeast two-hybrid, immunoprecipitation, and functional assays demonstrated a physical and functional interaction between Rrp1b and the previous identified metastasis modifier Sipa1. In parallel, using mouse and human metastasis gene expression data it was observed that extracellular matrix (ECM) genes are common components of metastasis predictive signatures, suggesting that ECM genes are either important markers or causal factors in metastasis. To investigate the relationship between ECM genes and poor prognosis in breast cancer, expression quantitative trait locus analysis of polyoma middle-T transgene-induced mammary tumor was performed. ECM gene expression was found to be consistently associated with Rrp1b expression. In vitro expression of Rrp1b significantly altered ECM gene expression, tumor growth, and dissemination in metastasis assays. Furthermore, a gene signature induced by ectopic expression of Rrp1b in tumor cells predicted survival in a human breast cancer gene expression dataset. Finally, constitutional polymorphism within RRP1B was found to be significantly associated with tumor progression in two independent breast cancer cohorts. These data suggest that RRP1B may be a novel susceptibility gene for breast cancer progression and metastasis.
Crawford
Nigel P S
NP
Laboratory of Population Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
Qian
Xiaolan
X
Ziogas
Argyrios
A
Papageorge
Alex G
AG
Boersma
Brenda J
BJ
Walker
Renard C
RC
Lukes
Luanne
L
Rowe
William L
WL
Zhang
Jinghui
J
Ambs
Stefan
S
Lowy
Douglas R
DR
Anton-Culver
Hoda
H
Hunter
Kent W
KW
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D015142:Baltimore; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D018450:Disease Progression; D004198:Disease Susceptibility; D005109:Extracellular Matrix / Q000235:genetics; D005260:Female; D020690:GTPase-Activating Proteins / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006239:Haplotypes; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D050505:Mutant Proteins / Q000378:metabolism; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D040641:Quantitative Trait Loci; D016019:Survival Analysis; D016896:Treatment Outcome
D051017:Apoptosis Regulatory Proteins; D002868:Chromosomal Proteins, Non-Histone; D020690:GTPase-Activating Proteins; D050505:Mutant Proteins; D009687:Nuclear Proteins; C107468:RRP1 protein, human; C574722:RRP1B protein, human; C091108:Sipa1 protein, mouse