Expression and function of the protein tyrosine phosphatase SHP-1 in oligodendrocytes

Massa, Paul T.; Saha, Sucharita; Wu, Chunchi; Jarosinski, Keith W.

doi:10.1002/(sici)1098-1136(20000215)29:4<376::aid-glia8>3.0.co;2-s

Cited by 52 publications

(73 citation statements)

References 48 publications

(47 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…30 It has been shown in oligodendrocytes from the motheaten mice, which have a genetic defect in the SHP-1 gene, that SHP-1 expression controls the activation of STAT3 by IL-6 signaling. 31 In this study, we examined SHP-1 in prostate cancer cell lines and in clinically well-annotated tumor tissue samples. We demonstrate that the prostatic cancer cell lines LNCaP and PC3 express SHP-1 mRNA and protein at different levels.…”

mentioning

confidence: 86%

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

Tassidis

Brokken

Jirström

et al. 2010

Intl Journal of Cancer

View full text Add to dashboard Cite

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.

show abstract

mentioning

confidence: 86%

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

Tassidis

Brokken

Jirström

et al. 2010

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…[30][31][32][33][34][35][36][37][38] The frequencies of expression intensities for NTRK1, NTRK1-pY674/ pY675, SHP-1, TP53, ER, HER2, PgR, and Ki-67 are summarized in Supplementary Table S2.…”

Section: Clinicopathological Parameters and Patient Outcomementioning

confidence: 99%

Phosphorylation of NTRK1 at Y674/Y675 induced by TP53-dependent repression of PTPN6 expression: A potential novel prognostic marker for breast cancer

Youssef¹,

Gillett

Agbaje

et al. 2014

Modern Pathology

View full text Add to dashboard Cite

We have identified a ligand-independent mechanism whereby the tumor suppressor, TP53, induces nerve growth factor receptor, NTRK1, phosphorylation at Y674/Y675 (NTRK1-pY674/pY675), via the repression of the NTRK1-phosphatase, PTPN6. This results in suppression of breast cancer cell proliferation. In this investigation, we aimed to establish whether perturbation of the wild-type TP53-NTRK1-pY674/pY675-PTPN6 pathway has an impact on disease-free survival of breast cancer patients without neo-adjuvant treatment. A total of 308 tumor samples were stained for NTRK1, NTRK1-pY674/pY675, PTPN6, and TP53 expression. Association between expression levels and disease-free survival was determined by the univariate/multivariate and Kaplan-Meir methods of analysis. DNA from tumors was sequenced to identify mutant or wild-type TP53. Tumors expressing NTRK1-pY674/pY675 but with undetectable or low levels of PTPN6 and TP53 were associated with prolonged 5, 10, and 15 years' disease-free survival by 48%, 36%, and 37%, respectively, in the multivariate analysis (Po0.05). A similar result was observed in tumors expressing wild-type TP53, NTRK1-pY674/pY675, and low or undetectable levels of PTPN6. Given that estrogen receptor-positive breast cancers encode wild-type TP53, we analyzed this expression pattern in these tumors. Multivariate analysis showed that it was significantly and independently predictive of prolonged survival by 66%, 70%, and 84%, respectively, (Po0.05). The Kaplan-Meir method demonstrated that NTRK1-pY674/pY675 together with undetectable or low levels of PTPN6 correlated with 59% probability of disease-free survival (median survival 15 years), compared with 7% probability of disease-free survival (median survival 4.5 years) when absent. In luminal A tumors, the presence of this pattern was estimated to have a 61% probability of disease-free survival (median survival 15 years), compared with 6% probability of disease-free survival (median survival 3 years) when it was absent. These results strongly suggest that expression of NTRK1-pY674/pY675 together with wild-type TP53 and low levels of PTPN6 expression are predictors of improved disease-free survival and that they could be useful biomarkers to predict clinical outcome. Breast cancer is a leading cause of early mortality among women. 1 The incidence varies worldwide, with developed countries having higher rates than developing countries. 1,2 Although the rate of breast cancer has continued to increase, 3 mortality rates have decreased, partly due to the enhanced use of diagnostic and screening techniques. 4,5

show abstract

“…Mixed glial cultures containing astrocytes, oligodendrocytes, and microglia were produced from brains of 8-day-old mice by a modified procedure as previously described (McCarthy and de Vellis 1980;Massa et al 2000). Briefly, brains were minced in Kreb's buffer with curved scissors into fine pieces.…”

Section: Glial Culturesmentioning

confidence: 99%

“…Loss of SHP-1 in the CNS as seen in motheaten (me/ me) mice leads to myelin pathology (Massa et al 2000(Massa et al , 2004 that may be caused by effects of an increased inflammatory milieu and/or specific alterations in cytokine signaling on the myelin-forming oligodendrocytes. Importantly, it was recently shown that leukocytes of MS patients have decreased levels of the phosphatase SHP-1, which results in increased inflammatory gene expression (Christophi et al 2008).…”

mentioning

confidence: 97%

“…We have previously shown that cytokines that act via the JAK/STAT pathway increase the expression of SHP-1 in mouse CNS glia (Massa et al 2000). These data, along with the observation that SHP-1 is crucial in regulating interferoninduced genes and fighting CNS viral infections led us to hypothesize that the SHP-1 gene may possess cytokineinducible promoter activity.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Promoter‐specific induction of the phosphatase SHP‐1 by viral infection and cytokines in CNS glia

Christophi¹,

Hudson²,

Gruber³

et al. 2008

Journal of Neurochemistry

Self Cite

View full text Add to dashboard Cite

We have previously shown that the protein tyrosine phosphatase SHP-1 is highly expressed in CNS glia and is an important modulator of cytokine signaling. As such, mice genetically lacking SHP-1 display constitutive myelin abnormalities, severe virus-induced demyelinating disease, and defects in innate anti-viral responses in the CNS. In this study, we show the differential distribution of the SHP-1 promoterspecific transcripts and demonstrate that several cytokines significantly induce SHP-1 expression in CNS glia. Consistent with these cytokine effects, infection with a neurotropic virus both in vitro and in vivo up-regulates SHP-1 transcripts and protein in CNS cells. Using CNS glial cultures of gene knockout mice, we show that interferons-b and interferons-c act through STAT-1 and interferon regulatory factor-1 to induce the SHP-1 promoter I transcripts. Conversely, interferons-b and IL-6 act through STAT-3 to induce SHP-1 promoter II transcripts. This study demonstrates that interferons and other cytokines associated with virus infections in the CNS can significantly induce the expression of SHP-1 through STAT-1/3 activity and provides a better understanding of the molecular mechanisms regulating cytokine-induced expression important for multiple homeostatic functions of SHP-1 in the CNS.

show abstract

Expression and function of the protein tyrosine phosphatase SHP-1 in oligodendrocytes

Cited by 52 publications

References 48 publications

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

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

Phosphorylation of NTRK1 at Y674/Y675 induced by TP53-dependent repression of PTPN6 expression: A potential novel prognostic marker for breast cancer

Promoter‐specific induction of the phosphatase SHP‐1 by viral infection and cytokines in CNS glia

Contact Info

Product

Resources

About