| Publication number |
CLPUB00457 |
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| Authors |
Wegener S., Mader A., Melzner I., Bruderlein S., Moller P. |
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| Title |
Lack of PTPN1 (PTP1B) in U-HO1, a new Hodgkin-derived cell line, protects cells from apoptosis. |
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| Citation |
Haematologica 92 Suppl. 5:39-39(2007) |
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| Web pages |
https://www.haematologica.org/content/92/supplement_5/1 |
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| Abstract |
Protein tyrosine phosphatases (PTPs), which catalyze dephosphorylation of
tyrosyl phosphorylated proteins, play an important role in cellular
signaling by serving as antagonists of Protein Tyrosine Kinases (PTKs).
PTPs regulate multiple cytokine and growth factor activated signaling
pathways which are associated with malignancies like myelodysplastic
syndromes and B-cell lymphomas. PTPN1 is a well studied nonreceptor
phophatase. JAK2 was shown to be a substrate of PTPN1 which results in a
negative regulation of the kinase activity of JAK2 and the subsequent
activation of downstream targets like STAT5. Furthermore it has been
demonstrated that PTPN1 is involved in regulation of apoptosis in
different cell systems. The parental tumor of U-HO1, a nodular sclerosing
classical Hodgkin lymphoma (cHL), and its resulting cell line proofed
negative for PTPN1 in Western blot and by immunomorphology. We hence
investigated the expression of PTPN1. PTPN1 cDNA (NM_002827) of U-HO1 was
markedly truncated: exon 2 to exon 8 were skipped translating into the
following predicted short protein of 26 amino acids:
MEMEKEFEQIDKSGSWAAIYQHESRH. To examine the role of lack in functional
PTPN1 we transfected U-HO1 cells with wt-PTPN1. Transient ectopic
expression of PTPN1 caused an increased dephosphorylation of phosphoSTAT5.
Stable wt-PTPN1 transfectants featured a very slow proliferation in
contrast to cells transfected with the empty vector. As evidenced by
Nicoletti staining and cytomorphology wt-PTPN1 undergo apoptosis to a much
greater extent than mock transfectants. To see whether PTPN1 deficiency is
occuring in the HRS-cells of cHL in vivo, we analyzed 61 samples from
patients with cHL by immunohistochemistry. Only 15 of 61 cHL samples
tested had PTPN1-positive neoplastic cells. Thus lack of PTPN1 is a common
feature in HRS-cells in vivo. In summary our results show that PTPN1 plays
a major role in deactivation of the JAK2-/STAT5 signaling pathway and its
deficiency saves HRS-cells from apoptosis.
|
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| Cell lines |
CVCL_2220; U-HO1 CVCL_UI40; U-HO1-PTPN1 |
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