Immunohistochemical detection of tyrosine phosphatase SHP‐1 predicts outcome after radical prostatectomy for localized prostate cancer

Abstract

The protein tyrosine kinase (PTK) receptors and cytosolic signaling proteins as well as the protein tyrosine phosphatases (PTPs) have important roles in regulation of growth of the benign and malignant prostate gland. Here, we studied expression of the protein tyrosine phosphatase SHP-1 in prostate cancer cell lines and in human prostatic tissues. SHP-1 is expressed at a high level in LNCaP prostate cancer cells compared with PC3 cells. Silencing of SHP-1 expression with siRNA in LNCaP cells led to an increased rate of proliferation, whereas overexpression of SHP-1 by means of transient and stable transfection in PC3 cells led to a decrease in proliferation. Corresponding changes were observed in cyclin D1 expression. We further demonstrate that LNCaP and PC3 cells respond differently to IL-6 stimulation. SHP-1 overexpression in PC3 cells reversed IL-6 stimulation of proliferation, whereas in SHP-1-silenced LNCaP cells, IL-6 inhibition of proliferation was not affected. In addition, IL-6 treatment led to higher levels of phosphorylated STAT3 in SHP-1-silenced LNCaP cells than in control cells. Next, SHP-1 expression in human prostate cancer was analyzed by immunohistochemical staining of tissue microarrays comprising tumor specimens from 100 prostate cancer patients. We found an inverse correlation between the tumor level of SHP-1 expression and time to biochemical recurrence and clinical progression among prostate cancer patients. In conclusion, our results suggest that a decreased level of SHP-1 expression in prostate cancer cells is associated with a high proliferation rate and an increased risk of recurrence or clinical progression after radical prostatectomy for localized prostate cancer.

Expression and function of ATIP/MTUS1 in human prostate cancer cell lines

“…SHP-1 is a well-known inhibitor of activation-promoting signaling cascades [35]. Recently, it was demonstrated that SHP-1 was expressed at higher levels in LNCaP than in PC3 cells and that silencing of SHP-1 expression in LNCaP cells led to an increased rate of proliferation, whereas, transfection and over expression of SHP-1 in PC3 cells decreased proliferation [36]. The results of our studies examining the knock-down and over-expression of ATIP in these two cell lines closely resemble those reported for SHP-1, except that the degree of silencing achieved with the LNCaP cell line was associated with an increase in sensitivity to EGF rather than an increase in absolute growth rate.…”

Alteration of SHP-1/p-STAT3 Signaling: A Potential Target for Anticancer Therapy

“…Some studies found decreased SHP-1 expression linked to poor outcome [115], whereas some concluded the opposite [116,117]. Immunohistochemical detection of SHP-1 has been shown to predict the outcome for localized prostate cancer; a decreased level of SHP-1 expression in prostate cancer cells is associated with a high proliferation rate and an increased risk of recurrence or clinical progression after radical prostatectomy for localized prostate cancer [115]. On the contrary, increased expression of SHP-1 is associated with local recurrence after radiotherapy for patients with nasopharyngeal carcinoma [117].…”

Prostate Cancer Dephosphorylation Atlas

“…A number of publications support an involvement of SHP-1 on negative regulation of cellular proliferation by SST (Lahlou et al, 2003). The expression of SHP-1 in rat prostate (Valencia et al, 1997) and in human prostate was shown as well (Tassidis et al, 2010). Despite the limitation of cell culture, some authors have defined SHP-1 as a decisive protein on determining cancer cell phenotype in vitro by using two classical prostate cancer cell lines: PC3 and LNCap.…”

“…In particular, tyrosine phosphorylation of key proteins is a critical event in the regulation of intracellular signaling pathways (Aoyama et al, 2003;Gee and Mansuy, 2004;Souza et al, 2009). There is strong evidence pointing that low SHP-1 PTP activity is associated with a high proliferation rate and an increased risk of recurrence after radical prostatectomy for localized prostate cancer (Tassidis et al, 2010). Moreover, it has been proposed that specific PTPs may be related to determining the developmental stage and aggressiveness degree of prostate cancer (Chuang et al, 2010).…”