title: Regulation of cell proliferation and migration by keratin19-induced nuclear import of early growth response-1 in breast cancer cells.
abstract: OBJECTIVE
  Keratin19 (KRT19) is the smallest known type I intermediate filament and is used as a marker for reverse transcriptase PCR-mediated detection of disseminated tumors. In this study, we investigated the functional analysis of KRT19 in human breast cancer.
  
  
  METHODS
  Using a short hairpin RNA system, we silenced KRT19 in breast cancer cells. KRT19 silencing was verified by Western blot analysis and immunocytochemistry. We further examined the effect of KRT19 silencing on breast cancer cells by cell proliferation, migration, invasion, colony formation assay, cell-cycle analysis, immunocytochemistry, immunohistochemistry, and mouse xenograft assay.
  
  
  RESULTS
  Silencing of KRT19 resulted in increased cell proliferation, migration, invasion, and survival. These effects were mediated by upregulation of Akt signaling as a result of reduced PTEN mRNA expression. Silencing of KRT19 decreased the nuclear import of early growth response-1 (Egr1), a transcriptional factor for PTEN transcription, through reduced association between Egr1 and importin-7. We also confirmed that silencing of KRT19 increased tumor formation in a xenograft model.
  
  
  CONCLUSIONS
  KRT19 is a potential tumor suppressor that negatively regulates Akt signaling through modulation of Egr1 nuclear localization.
authors.affiliation: Department of Life Science, Hanyang University, Seoul, Republic of Korea.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Ju
authors.forename: Wonseok
authors.initials: W
authors.lastname: Yang
authors.forename: Kyung-Min
authors.initials: KM
authors.lastname: Lee
authors.forename: Sunhwa
authors.initials: S
authors.lastname: Oh
authors.forename: KeeSoo
authors.initials: K
authors.lastname: Nam
authors.forename: Sarah
authors.initials: S
authors.lastname: Shim
authors.forename: Soon Young
authors.initials: SY
authors.lastname: Shin
authors.forename: Myung Chan
authors.initials: MC
authors.lastname: Gye
authors.forename: In-Sun
authors.initials: IS
authors.lastname: Chu
authors.forename: Incheol
authors.initials: I
authors.lastname: Shin
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D051766:Early Growth Response Protein 1 / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D064593:Heterografts; D006801:Humans; D028884:Karyopherins / Q000378:metabolism; D053539:Keratin-19 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D051766:Early Growth Response Protein 1; C466996:IPO7 protein, human; D028884:Karyopherins; D053539:Keratin-19; D018160:Receptors, Cytoplasmic and Nuclear; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase