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

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摘要：

SHP-1, an SH2 domain-containing protein tyrosine phosphatase, is primarily expressed in hematopoietic cells and behaves as a key regulator controlling intracellular phosphotyrosine levels in lymphocytes. SHP-1 has been proposed as a candidate tumor suppressor gene in lymphoma, leukemia and other cancers, as it functions as an antagonist to the growth-promoting and oncogenic potentials of tyrosine kinase. The decreased levels of SHP-1 protein and SHP-1 mRNA observed in various leukemia and lymphoma cell lines have been attributed to either the methylation of the promoter region of the SHP-1 gene or the post-transcriptional block of SHP-1 protein synthesis. In contrast, SHP-1 protein is normally or over-expressed in some non-lymphocytic cell lines, such as prostate cancer, ovarian cancer and breast cancer cell lines. SHP-1 expression also is decreased in some breast cancer cell lines with negative expression of estrogen receptor as well as some prostate and colorectal cancer cell lines. These data suggest that SHP-1 can play either negative or positive roles in regulating signal transduction pathways. Dysfunction in SHP-1 regulation can cause abnormal cell growth and induce different kinds of cancers. In this paper, we summarize recent studies on the expression and regulation of SHP-1 protein and its pathological function in the development of lymphoma, leukemia and other cancers.

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SHP-1 Tumor suppressor gene Regulation Cancer ALCL, anaplastic large-cell lymphoma AML, acute myeloblastic leukemia APL, acute promyelocytic leukemia ATL, acute T lymphoblastic leukemia ATLL, adult T cell lymphoma/leukemia B-ALL, T-lineage acute lymphoblastic leukemia BCR, B cell receptor B-LY, B-cell lymphoma CLL/SLL, chronic lymphocytic leukemia/small lymphocytic lymphoma CML, chronic myelogenous leukemia CTCL, cutaneous T cell lymphoma DLL, diffuse large B cell lymphoma EBV, Epstein&ndash Barr virus ER, estrogen receptor FCCL, follicle center cell lymphoma FL, follicular lymphoma HCL, hairy cell leukemia HD, Hodgkin's disease HTLV-I, human T cell lymphotropic virus type I ITIM, immunoreceptor tyrosine-based inhibition motif JAK, Janus activated kinases MCL, mantle cell lymphoma MM, multiple myeloma MZL, maginal zone lymphoma NK/T-LY, natural killer/T lymphoma PBL, peripheral blood lymphocyte PCR, polymerase chain reaction PT, peripheral T cell lymphoma PTK, protein tyrosine kinase PTP, protein tyrosine pho