title: Immunohistochemical evaluation of ROCK activation in invasive breast cancer.
abstract: BACKGROUND
  Two isoforms of Rho-associated coiled-coil kinase (ROCK), ROCKI and ROCKII, play an important role in many cellular processes. Despite the accumulating evidence showing that ROCK could be a potential cancer therapeutic target, the relevant tumor types to ROCK activation are not well clarified. The aim of this study was to evaluate the ROCK activation status in different tumor types of breast cancer.
  
  
  RESULTS
  We evaluated the immunoreactivities of phosphorylation-specific antibodies of ROCKI and ROCKII to inform their kinase activation in 275 of breast carcinoma tissues, including 56 of carcinoma in situ, 116 of invasive carcinoma, and 103 of invasive carcinoma with metastasis. ROCKII activation signal detected in nucleus was significantly correlated with tumor metastasis, while ROCKI and cytosolic ROCKII activation signals made no significant difference in that metastasis. Furthermore, nuclear ROCKII activation signal was associated with poor clinical outcome and correlated with late tumor stage, low expression of estrogen receptor (ER) and progesterone receptor (PR), overexpression of human epidermal growth factor receptor 2 (HER2) and high Ki67 labeling index.
  
  
  CONCLUSIONS
  Nuclear ROCKII activation signal might contribute to the tumor metastasis in breast cancer. Differences in ROCK activation that underlie the phenotypes of breast cancer could enhance our understanding for the use of ROCK inhibitors in cancer therapy.
authors.affiliation: Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd, Taipei, Taiwan ROC. cyhsu@vghtpe.gov.tw.|Department of Pathology, National Yang-Ming University School of Medicine, No. 155, Sec. 2, Linong St, Taipei, Taiwan ROC. cyhsu@vghtpe.gov.tw.
authors.forename: Chih-Yi
authors.initials: CY
authors.lastname: Hsu
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, No. 155, Sec. 2, Linong St, Taipei, Taiwan ROC. zfchang@ym.edu.tw.
authors.forename: Zee-Fen
authors.initials: ZF
authors.lastname: Chang
authors.affiliation: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, 11221 No. 155, Sec. 2, Linong Street, Taipei, Taiwan ROC. hhl@ym.edu.tw.
authors.forename: Hsiao-Hui
authors.initials: HH
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D002467:Cell Nucleus / Q000201:enzymology*; D004789:Enzyme Activation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: C515851:ROCK1 protein, human; C515852:ROCK2 protein, human; D054460:rho-Associated Kinases