The function of the protein tyrosine phosphatase SHP-1 in cancer

Wu, Chengyu; Sun, Mingzhong; Liu, Lijun; Zhou, G.T.

doi:10.1016/s0378-1119(03)00400-1

Cited by 269 publications

(244 citation statements)

References 59 publications

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“…The loss or diminished expression of SHP1 observed in leukemias and lymphomas (33) suggest that SHP1 function plays a vital role in the suppression of undesired cell proliferation. In contrast to hematopoietic tumors, SHP1 mRNA was reported to be increased in estrogen receptor-positive and -negative breast cancer cell lines and in 58% of the primary breast tumors compared with normal breast cells (23). These observations support our results showing increased levels of SHP1 expression in breast adenocarcinoma cells and cell lines.…”

Section: Discussionsupporting

confidence: 90%

“…Low expression of SHP1 in normal epithelial cells contrasts with dramatically upregulated SHP1 expression in several human tumors including epithelial breast and ovarian tumors (20,23,24) suggesting a potential role for SHP1 in modulation of tumor cell proliferation. The molecular mechanisms underlying the upregulated expression of SHP1 in epithelial tumors have not been determined.…”

Section: Introductionmentioning

confidence: 99%

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Breast Cancer Cells Proliferation Is Regulated by Tyrosine Phosphatase SHP1 through c-jun N-Terminal Kinase and Cooperative Induction of RFX-1 and AP-4 Transcription Factors

Amin

Kumar

Nilchi

et al. 2011

Molecular Cancer Research

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In this study, we show that proliferation of breast cancer cells is suppressed by IGF-1-activated JNK MAPK pathway. The molecular mechanism by which c-jun-NH,-kinase (JNK) activation induces antiproliferative signals in IGF-1-stimulated breast cancer cells remains unknown. Tyrosine phosphatase SHP1 is known to negatively regulate signal transduction pathways activated by cell surface receptors including IGF-1. Moreover, SHP1 transcript and protein levels are increased in epithelial tumors. Therefore, we hypothesized that IGF-activated JNK induces expression of SHP1 in breast cancer cells. To further clarify the role of SHP1 in tumor growth, we correlated the proliferation rates of breast adenocarcinoma cells with SHP1 expression and JNK activation. We show that proliferation of serum-or IGF-1-stimulated breast adenocarcinoma cells is negatively regulated by SHP1 and show for the first time that IGF-1-activated JNK induces SHP1 expression in MCF-7 cells used as experimental model. In an attempt to understand the mechanism by which serum-or IGF-1-activated JNK induces SHP1 expression resulting in suppression of cell proliferation, we reveal for the first time that in serum-or IGF-1-stimulated breast cancer MCF-7 cells, JNK induces SHP1 expression through the binding of AP-4 and RFX-1 transcription factors to the epithelial tissue-specific SHP1 promoter. Overall, we show for the first time that IGF-1-stimulated proliferation of breast adenocarcinoma cells is negatively regulated by SHP1 through activation of JNK. Mol Cancer Res; 9(8); 1112-25. Ó2011 AACR.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Breast Cancer Cells Proliferation Is Regulated by Tyrosine Phosphatase SHP1 through c-jun N-Terminal Kinase and Cooperative Induction of RFX-1 and AP-4 Transcription Factors

Amin

Kumar

Nilchi

et al. 2011

Molecular Cancer Research

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“…Interestingly, PTPN6 is normally expressed or overexpressed in some nonlymphocytic cell lines such as prostate, ovarian, and breast cancer cell lines. The level of PTPN6 expression is also altered in some breast cancer cell lines with negative expression of estrogen receptor, and in some prostate and colorectal cancer cell lines (25). MEIS2 belongs to a group of homeobox cofactors for HOX-class homeobox proteins, which control growth and differentiation during embryogenesis and homeostasis, and has been implicated in various cancer types.…”

Section: Discussionmentioning

confidence: 99%

Long-Range Epigenetic Silencing Associates with Deregulation of Ikaros Targets in Colorectal Cancer Cells

Javierre

Rodríguez-Ubreva

Al‐Shahrour

et al. 2011

Molecular Cancer Research

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Transcription factors are common targets of epigenetic inactivation in human cancer. Promoter hypermethylation and subsequent silencing of transcription factors can lead to further deregulation of their targets. In this study, we explored the potential epigenetic deregulation in cancer of Ikaros family genes, which code for essential transcription factors in cell differentiation and exhibit genetic defects in hematologic neoplasias. Unexpectedly, our analysis revealed that Ikaros undergoes very specific promoter hypermethylation in colorectal cancer, including in all the cell lines studied and around 64% of primary colorectal adenocarcinomas, with increasing proportions in advanced Duke's stages. Ikaros hypermethylation occurred in the context of a novel long-range epigenetic silencing (LRES) region. Reintroduction of Ikaros in colorectal cancer cells, ChIP-chip analysis, and validation in primary samples led us to identify a number of direct targets that are possibly related with colorectal cancer progression. Our results not only provide the first evidence that LRES can have functional specific effects in cancer but also identify several deregulated Ikaros targets that may contribute to progression in colorectal adenocarcinoma.

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“…Decreased or abolished expression in leukemia and lymphoma has been related to both malignant transformation and tumor cell invasiveness. [12][13][14] Moreover, SHP-1 expression in leukemic cells can lead to decreased proliferation and induction of morphological changes. 15 Transient transfection of SHP-1 in the breast cancer cell line MDA-MB-231, with undetectable endogenous SHP-1, reduced cell proliferation 2-3 fold.…”

mentioning

confidence: 99%

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

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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.

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The function of the protein tyrosine phosphatase SHP-1 in cancer

Cited by 269 publications

References 59 publications

Breast Cancer Cells Proliferation Is Regulated by Tyrosine Phosphatase SHP1 through c-jun N-Terminal Kinase and Cooperative Induction of RFX-1 and AP-4 Transcription Factors

Breast Cancer Cells Proliferation Is Regulated by Tyrosine Phosphatase SHP1 through c-jun N-Terminal Kinase and Cooperative Induction of RFX-1 and AP-4 Transcription Factors

Long-Range Epigenetic Silencing Associates with Deregulation of Ikaros Targets in Colorectal Cancer Cells

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

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