Study On The Expression Of T Cell Protein Tyrosine Phosphatase TC-PTP In Cancer Tissues

Protein tyrosine phosphatases (PTPs) and protein tyrosine kinases that are coordinately implicated in cell signaling transduction are closely associated with numerous physiologic and pathologic phenomenon such as tumors, cardiac and vascular diseases, immune disorders, contagion, nervous and metabolic diseases. TC-PTP (T cell-protein tyrosine phosphatase) , one of the first PTPs identified following the original purification of PTP-1B was cloned from a human peripheral T-cell cDNA library in 1989.TC-PTP has become an important member of the PTPs family in two aspects. Firstly, TC-PTP has been reported to act on downstream signaling events initiated by the epidermal growth receptor, suggesting that it may act as an important modulator of receptor tyrosine kinases and mitogenic signaling. Secondly, the finding of immune deficiency and lethality observed in TC-PTP null mice emphasizes the importance of this small PTP in the hematopoietic system. Although much remains to be uncovered, some recent findings on the function of this small PTP suggest that it play a critical role in regulating mammalian cell signaling.A role for TC-PTP in oncogenesis is currently emerging. Overexpression of a truncated form of TC-PTP lacking the nuclear localization sequence could revert the transformed phenotype of Rat2 cells stably expressing v-fms, as well as inhibiting the potential of these cells to induce tumor growth in nude mice. Then, Delta EGFR, a truncated form of the EGFR expressed in U87MG glioblastoma cells, was found to be a substrate of TC-PTP. Furthermore, overexpression of TC-PTP in U87MG cells inhibited proliferation and anchorage-independent growth in vitro, as well as suppressing the tumorigenicity of Delta EGFR expressing glioblastoma cells implanted in mice.In TC-PTP null fibroblasts, these cells presented delayed activation of NF-kB, suggesting that TC-PTP might exert a positive regulatory effect in enhancing the NF-kB signaling pathway. The ability of NF-kB to stimulate cell proliferation and to prevent apoptosis can undoubtedly favor cancer development, and activation of NF-kB has been linked with many human cancers, In other types of cancer, such as colon cancer, decreased activity of NF-kB is associated with tumorigenesis. Thus, regulation of NF-kB activity, whether positive or negative, appears to be an important determinant of oncogenicity. In this aspect, TC-PTP could potentially be involved in the regulation of NF-kB pro-tumorigenic activity.Based on these findings, TC-PTP seems to play a negative role in tumorigenesis and play a positive regulator of cell proliferation. Further analysis of TC-PTP expression in human cancer cells and tissues will help to elucidate and define the role of this enzyme in oncogenesis.â–³TC-PTP gene (catalytic domain of TC-PTP) was amplified by PCR. After the dissoluble expression, the protein ofâ–³TC-PTP was separated and purified. And then, the antiserum was prepared by immunizing rabbit with the purified recombinationâ–³TC-PTP. Rabbit polyclonal antibody againstâ–³TC-PTP was purified by PVDF immobilized antigen affinity chromatography. It played a foundational role in further studying the physiological function of TC-PTP and associated cell signal transduction. Imrnunohistochemical staining of several kinds of cancer tissues was performed using the antibody againstâ–³TC-PTP to confirm the expression ofâ–³TC-PTP in these tissues. It offered a new...