title: Phosphorylation of p90RSK is associated with increased response to neoadjuvant chemotherapy in ER-positive breast cancer.
abstract: BACKGROUND
  The clinical implication of Ras/Raf/ERK pathway activity in breast cancer tissue and its association with response to chemotherapy is controversial. We aimed to explore the value of p90RSK phosphorylation, a downstram molecule of the pathway, in predicting chemotherapy response in breast cancer.
  
  
  METHODS
  The expression of phosphorylated p90RSK (phospho-p90RSK) and chemotherapy response was measured in 11 breast cancer cell lines and 21 breast cancer tissues. The predictive value of phospho-p90RSK was validated in core needle biopsy specimens of 112 locally advanced breast cancer patients who received anthracycline and taxane-based neoadjuvant chemotherapy.
  
  
  RESULTS
  In 11 breast cancer cell lines, the relative expression of phospho-p90RSK was inversely correlated with cell survival after doxorubicin treatment (p = 0.021). Similar association was observed in fresh tissues from 21 breast cancer patients in terms of clinical response. In paraffin-embedded, formalin-fixed tissues from core needle biopsy tissues from 112 patients, positive phospho-p90RSK expression was associated with greater tumor shrinkage and smaller post-chemotherapy tumor size. The association between phospho-p90RSK expression and chemotherapy response was more evident in estrogen receptor(ER)-positive tumors. The expression of phosphor-p90RSK did not show a significant relationship with the incidence of pCR. P90RSK silencing using siRNA did not affect the cancer cell's response to doxorubicin, and the expression of phospho-p90RSK was highly correlated with other Ras/Raf/ERK pathway activation.
  
  
  CONCLUSIONS
  Our results suggest that phospho-p90RSK expression, which reflects the tumor's Ras/Raf/ERK/p90RSK pathway activation can be a potential predictive marker for chemotherapy response in ER-positive breast cancer which needs further independent validation.
authors.affiliation: Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hyeong-Gon
authors.initials: HG
authors.lastname: Moon
authors.forename: Jae Kyo
authors.initials: JK
authors.lastname: Yi
authors.forename: Hee Sung
authors.initials: HS
authors.lastname: Kim
authors.forename: Hea Young
authors.initials: HY
authors.lastname: Lee
authors.forename: Kyung-Min
authors.initials: KM
authors.lastname: Lee
authors.forename: Minju
authors.initials: M
authors.lastname: Yi
authors.forename: Sookyung
authors.initials: S
authors.lastname: Ahn
authors.forename: Hee-Chul
authors.initials: HC
authors.lastname: Shin
authors.forename: Ji-hyun
authors.initials: JH
authors.lastname: Ju
authors.forename: Incheol
authors.initials: I
authors.lastname: Shin
authors.forename: Wonshik
authors.initials: W
authors.lastname: Han
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Noh
mesh_terms: D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D010766:Phosphorylation; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D018943:Anthracyclines; D011960:Receptors, Estrogen; D043823:Taxoids; D004317:Doxorubicin; D038744:Ribosomal Protein S6 Kinases, 90-kDa