title: The Clinical Implications of RSK1-3 in Human Breast Cancer.
abstract: OBJECTIVE
  The ribosomal S6 protein kinase (RSK) family is an important effector of extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) that could influence tumour metastasis by phosphorylating proteins in both the nuclear and cytoplasmic compartments. Aberrant expression of RSK is evident in certain malignancies but the role played by RSK in breast cancer is still not clear. This study aimed to examine the expression of RSK in human breast cancer specimens and its role to breast cancer metastasis.
  
  
  METHODS
  The expression of RSK1 to -3 were separately examined in human breast cancer tissues (normal, n=33; cancer, n=112) using quantitative real-time polymerase chain reaction (Q-PCR) and immunohistochemistry. Migration and adhesion of breast cancer cells treated with the RSK inhibitor SL0101 were investigated by electric cell impedance sensing (ECIS). The effect on growth and invasion of RSK1-3 was then investigated using in vitro models.
  
  
  RESULTS
  The clinical data and immunohistochemistry revealed that expression of RSK1 and RSK3 were less in tumour tissues than normal. mRNA expression of RSK2 was negatively correlated with grade, TNM staging, and survival rate. SL0101 inhibited adhesion of the MCF-7 and MDA-231 breast cancer cell lines. SL0101 suppressed MDA-231 invasion and the alternate RSK inhibitor BRD7389 inhibited the invasion of MCF-7 and MDA-231 cells.
  
  
  CONCLUSIONS
  RSK1 and 3 but not RSK2 are down-regulated in breast tumour and are associated with disease progression. RSK may be a key component in the progression and metastasis of breast cancer.
authors.affiliation: Cardiff-China Medical Research Collaborative, Cardiff University School of Medicine, Heath Park, Cardiff, U.K. Department of Biochemistry and Molecular Biology, Basic Medicine School, Cancer Institute of Capital Medical University, Beijing, P.R. China Capital Medical University-Cardiff University Joint Centre for Biomedical Research; Beijing International Cooperation Base for Science and Technology on China-UK Cancer Research, Capital Medical University, Beijing, P.R. China Beijing Key Laboratory for Cancer Invasion and Metastasis Research, Beijing, P.R. China.
authors.forename: Huishan
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Cardiff-China Medical Research Collaborative, Cardiff University School of Medicine, Heath Park, Cardiff, U.K. martinta1@cf.ac.uk.
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Martin
authors.affiliation: Cardiff-China Medical Research Collaborative, Cardiff University School of Medicine, Heath Park, Cardiff, U.K.
authors.forename: Eleri L
authors.initials: EL
authors.lastname: Davies
authors.affiliation: Cardiff-China Medical Research Collaborative, Cardiff University School of Medicine, Heath Park, Cardiff, U.K.
authors.forename: Fiona
authors.initials: F
authors.lastname: Ruge
authors.affiliation: Department of Biochemistry and Molecular Biology, Basic Medicine School, Cancer Institute of Capital Medical University, Beijing, P.R. China Capital Medical University-Cardiff University Joint Centre for Biomedical Research; Beijing International Cooperation Base for Science and Technology on China-UK Cancer Research, Capital Medical University, Beijing, P.R. China Beijing Key Laboratory for Cancer Invasion and Metastasis Research, Beijing, P.R. China.
authors.forename: Hefen
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Biochemistry and Molecular Biology, Basic Medicine School, Cancer Institute of Capital Medical University, Beijing, P.R. China Capital Medical University-Cardiff University Joint Centre for Biomedical Research; Beijing International Cooperation Base for Science and Technology on China-UK Cancer Research, Capital Medical University, Beijing, P.R. China Beijing Key Laboratory for Cancer Invasion and Metastasis Research, Beijing, P.R. China.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Basic Medicine School, Cancer Institute of Capital Medical University, Beijing, P.R. China Capital Medical University-Cardiff University Joint Centre for Biomedical Research; Beijing International Cooperation Base for Science and Technology on China-UK Cancer Research, Capital Medical University, Beijing, P.R. China Beijing Key Laboratory for Cancer Invasion and Metastasis Research, Beijing, P.R. China.
authors.forename: X U
authors.initials: XU
authors.lastname: Teng
authors.affiliation: Cardiff-China Medical Research Collaborative, Cardiff University School of Medicine, Heath Park, Cardiff, U.K.
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002448:Cell Adhesion; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D018572:Disease-Free Survival; D017097:Electric Impedance; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D061986:MCF-7 Cells; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D047428:Protein Kinase Inhibitors; C069329:RPS6KA1 protein, human; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C069330:ribosomal protein S6 kinase, 90kDa, polypeptide 3
keywords: Metastasis suppressor gene; RSK; SL0101; adhesion; breast tumour; immunohistochemistry; invasion