title: RecQL4 helicase amplification is involved in human breast tumorigenesis.
abstract: Breast cancer occur both in hereditary and sporadic forms, and the later one comprises an overwhelming majority of breast cancer cases among women. Numerical and structural alterations involving chromosome 8, with loss of short arm (8p) and gain of long arm (8q), are frequently observed in breast cancer cells and tissues. In this study, we show that most of the human breast tumor cell lines examined display an over representation of 8q24, a chromosomal locus RecQL4 is regionally mapped to, and consequently, a markedly elevated level of RecQL4 expression. An increased RecQL4 mRNA level was also observed in a majority of clinical breast tumor samples (38/43) examined. shRNA-mediated RecQL4 suppression in MDA-MB453 breast cancer cells not only significantly inhibit the in vitro clonogenic survival and in vivo tumorigenicity. Further studies demonstrate that RecQL4 physically interacts with a major survival factor-survivin and its protein level affects survivin expression. Although loss of RecQL4 function due to gene mutations causally linked to occurrence of human RTS with features of premature aging and cancer predisposition, our studies provide the evidence that overexpression of RecQL4 due to gene amplification play a critical role in human breast tumor progression.
authors.affiliation: Laboratory of Disease Genomics and Individualized Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Fang
authors.forename: Linghu
authors.initials: L
authors.lastname: Nie
authors.forename: Zhenfen
authors.initials: Z
authors.lastname: Chi
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Dan
authors.initials: D
authors.lastname: Guo
authors.forename: Xuemei
authors.initials: X
authors.lastname: Lu
authors.forename: Tom K
authors.initials: TK
authors.lastname: Hei
authors.forename: Adayabalam S
authors.initials: AS
authors.lastname: Balajee
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D056426:Genetic Loci / Q000235:genetics; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D053484:RecQ Helicases / Q000172:deficiency / Q000235:genetics*; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D034741:RNA, Small Interfering; D000077022:Survivin; D053484:RecQ Helicases
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