Abstract P2-07-08: Receptor Like Protein Tyrosin Phosphatases kappa (PTPRK), Its Pattern of Expression in Clinical Breast Cancer and Biological Impact on Breast Cancer Cells
Authors: Sun P-H , Ye L , Mansel RE , Jiang WG. 
Published: April 2011

Background:

PTPs are signaling molecules which regulate cell growth, differentiation and oncogenic transformation. PTPRK, receptor-type protein tyrosine phosphatase kappa, is known to down-regulate the transcriptional activity of beta-catenin and impact distribution of beta-catenin/E-cadherin complexes in cancer cell membrane. However, the role played by PTPRK in cancer remains largely unknown. In present study, expression of PTPRK was assessed in a breast cancer cohort and its association with clinical parameters and the impact of PTPRK on cell functions were further analysed. Methods:

Expression of PTPRK was examined in a cohort of 33 normal breast tissue and 127 primary breast tumour tissue samples. Transcript levels of PTPRM were then determined using quantitative real time-PCR and protein levels were assessed using immunohistochemical (IHC) staining. The association of PTPRM transcripts level and pathological and clinical aspects was then analysed. Ribozyme transgenes were constructed to knock-down PTPRK expression in MDA-MB-231 cells. The effect this had on in vitro cell growth, invasion and adhesion was examined using a variety of in vitro function assays.

Result:

IHC staining of PTPRK was seen generally distributed in the breast tissues, including tumours and normal background tissues. A stronger staining was revealed in cytoplasm of both mammary epithelia and cancer cells in comparison with the surrounding stroma and lipocytes. PTPRK expression levels were lower in patient samples with a Nottingham Prognosis Index (NPI) greater than 5.4 (poor prognosis group) (21029±54355) compared to those with NPI &lt;3.4 (good prognosis group) (101232±257009, p=0.039). PTPRK transcript levels were decreased in patients died from breast cancer, being 10392±30736, p=0.0075 when compared with that of patients being disease free (93337±253376). The expression of PTPRK transcripts was significantly associated with disease free survival. The patients with lower expression of PTPRK had shorter survival (median=122.0 months, 95%CI=105.3-138.6), p=0.016 vs. that of patients with higher expression levels (median= 138.8 months, 95%CI=130.1-147.5months). Knocking down of PTPRK in MDA-MB-231 cells (MDA-MB-231PTPRK) resulted an increase in cell growth, adhesion and invasion in vitro. The growth rate of MDA-MB-231 PTPRK was 2181±90, P&lt;0.001 compared with MDA-MB-231pEF controls (1472±50). The adhesive cell number of MDA-MB-231PTPRK was 169.75±20.59, P&lt;0.001 compared with MDA-MB-23pEF (91±21.33) controls. The invaded cell number of MDA-MB-231PTPRK was 193±12.5, P&lt;0.001 compared with MDA-MB-231pef (149±16.6) controls. Conclusion: The expression of PTPRK transcripts was decreased in the poor prognostic breast tumours compared with those with good prognosis. The decreased PTPRK transcript levels were correlated with poorer disease free survival. Knockdown of PTPRK in breast cancer resulted increases in cell growth, adhesion and invasion. Together with its association with prognosis, it has been suggested that PRPRK plays inhibitory roles during the disease progression of breast cancer.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-07-08.