title: Low expression of SHP-2 is associated with less favorable prostate cancer outcomes.
abstract: Src homology 2 domain-containing tyrosine phosphatase-2 (SHP-2) is an important regulator of cell signaling because of its ability to dephosphorylate receptors of growth factors as well as the cytokines and tyrosine-phosphorylated proteins associated with these receptors. In the current study, we used four different prostate cancer cell lines: PC3, DU145, LNCaP and LNCaP-IL6+. Tumor specimens from 122 patients with prostate cancer were analyzed using a tissue microarray. Our data demonstrate that all four prostate cancer cell lines express the SHP-2 protein. Additionally, low staining intensity and SHP-2 expression in the cytoplasm of cancer cells in prostate tumor specimens was inversely correlated with prostate volume (p = 0.041 and p = 0.042, respectively) whereas nuclear staining was positively correlated with extracapsular extension (p = 0.039). In our post-prostatectomy specimens, we found that patients with low SHP-2 expression had less favorable outcomes with respect to biochemical recurrence and clinical progression (p = 0.005 and p = 0.018, respectively). The loss of cytoplasmic SHP-2 expression is associated with increased growth and prostatic cancer progression.
authors.affiliation: Department of Laboratory Medicine, Division of Tumor Biology, Lund University, Lund, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Tassidis
authors.forename: Leon J S
authors.initials: LJ
authors.lastname: Brokken
authors.forename: Karin
authors.initials: K
authors.lastname: Jirström
authors.forename: Anders
authors.initials: A
authors.lastname: Bjartell
authors.forename: David
authors.initials: D
authors.lastname: Ulmert
authors.forename: Pirkko
authors.initials: P
authors.lastname: Härkönen
authors.forename: Anette Gjörloff
authors.initials: AG
authors.lastname: Wingren
mesh_terms: D000368:Aged; D003593:Cytoplasm / Q000378:metabolism*; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010766:Phosphorylation; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism*; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism; D015996:Survival Rate; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured
chemical_list: C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11