title: LATS2 is a modulator of estrogen receptor alpha.
abstract: BACKGROUND
  Estrogen Receptor α (ERα), a member of the nuclear receptor superfamily of transcription factors, plays a central role in breast cancer development. More than two-thirds of patients with breast cancer are ERα-positive; however, a proportion becomes resistant. Phosphorylation of ERα is one of the mechanisms associated with resistance to endocrine therapy. In a kinome screen, we have identified the large tumor suppressor homolog-2 (LATS2) as a potential kinase, acting on ERα.
  
  
  METHODS
  The role of LATS2 on activation of ERα transcription and its functional consequences was examined by various molecular and cellular biology techniques.
  
  
  RESULTS
  LATS2 co-localises with ERα in the nucleus. LATS2-silencing increases expression of ERα-regulated genes and inhibits proliferation. At the protein level, inhibition of LATS2 reduces the expression of cyclin-D1 and Nuclear Receptor Co-Repressor (NCoR) while increasing the expression of p27.
  
  
  CONCLUSIONS
  Identifying novel kinases which modulate ERα activity is relevant to therapeutics. LATS2 modulates ERα-regulated gene transcription, through direct and/or indirect interactions with ERα.
authors.affiliation: Department of Surgery & Cancer, Imperial College, Hammersmith Hospital Campus, Du Cane Road, London, W12 0NN, UK.
authors.forename: Lei Cheng
authors.initials: LC
authors.lastname: Lit
authors.forename: Susan
authors.initials: S
authors.lastname: Scott
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Justin
authors.initials: J
authors.lastname: Stebbing
authors.forename: Andrew
authors.initials: A
authors.lastname: Photiou
authors.forename: Georgios
authors.initials: G
authors.lastname: Giamas
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D056971:Nuclear Receptor Co-Repressor 1 / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015533:Transcriptional Activation; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D047628:Estrogen Receptor alpha; C539127:NCOR1 protein, human; D056971:Nuclear Receptor Co-Repressor 1; D018809:Proliferating Cell Nuclear Antigen; D025521:Tumor Suppressor Proteins; C413374:p27 antigen; C406449:LATS2 protein, human; D017346:Protein Serine-Threonine Kinases