title: The cyclin-like protein Spy1/RINGO promotes mammary transformation and is elevated in human breast cancer.
abstract: BACKGROUND
  Spy1 is a novel 'cyclin-like' activator of the G1/S transition capable of enhancing cell proliferation as well as inhibiting apoptosis. Spy1 protein levels are tightly regulated during normal mammary development and forced overexpression in mammary mouse models accelerates mammary tumorigenesis.
  
  
  METHODS
  Using human tissue samples, cell culture models and in vivo analysis we study the implications of Spy1 as a mediator of mammary transformation and breast cancer proliferation.
  
  
  RESULTS
  We demonstrate that this protein can facilitate transformation in a manner dependent upon the activation of the G2/M Cdk, Cdk1, and the subsequent inhibition of the anti-apoptotic regulator FOXO1. Importantly, we show for the first time that enhanced levels of Spy1 protein are found in a large number of human breast cancers and that knockdown of Spy1 impairs breast cancer cell proliferation.
  
  
  CONCLUSIONS
  Collectively, this work supports that Spy1 is a unique activator of Cdk1 in breast cancer cells and may represent a valuable drug target and/or a prognostic marker for subsets of breast cancers.
authors.affiliation: Faculty of Pharmacy, Al Zyatoona Private University, Amman, Jordan.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Al Sorkhy
authors.forename: Rosa-Maria
authors.initials: RM
authors.lastname: Ferraiuolo
authors.forename: Espanta
authors.initials: E
authors.lastname: Jalili
authors.forename: Agnes
authors.initials: A
authors.lastname: Malysa
authors.forename: Andreea R
authors.initials: AR
authors.lastname: Fratiloiu
authors.forename: Bonnie F
authors.initials: BF
authors.lastname: Sloane
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Porter
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D016203:CDC2 Protein Kinase / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000502:physiology; D055785:Gene Knockdown Techniques; D006801:Humans; D015674:Mammary Neoplasms, Animal / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D046228:Microarray Analysis; D041681:NIH 3T3 Cells; D014407:Tumor Cells, Cultured
chemical_list: D018797:Cell Cycle Proteins; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C486530:SPDYA protein, human; C529672:Spy1 protein, mouse; D016203:CDC2 Protein Kinase