Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic metastasis is a major factor in limiting the prognosis of patients with colon carcinoma. Recent investigations indicate a correlation between plasminogen activator profiles and hepatic metastasis. We examined the effectiveness of tissue plasminogen activator (tPA) gene therapy using a hepatic metastasis model of murine colon carcinoma. Murine colon carcinoma Colon 26 cells transduced with an MFGtPA retroviral vector (Colon 26/tPA) or an MFGLacZ retroviral vector (Colon 26/LacZ) were injected into the liver via the superior mesenteric vein of BALB/c mice, whose survival rates were checked daily. The mean survival rate of mice with hepatic metastasis induced by Colon 26/LacZ was 23.1 days, whereas that of mice with Colon 26/tPA was >100 days. The in vitro proliferation of Colon 26/tPA was comparable with that of Colon 26/LacZ, and antitumor immunity to wild-type Colon 26 cells was not induced after an intrahepatic injection of Colon 26/tPA. We suggest that transduction of the tPA gene to murine colon cancer is useful against the establishment of hepatic metastasis.
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PMID:Inhibitory effect on the establishment of hepatic metastasis by transduction of the tissue plasminogen activator gene to murine colon cancer. 1041 57

Among mammalian secreted phospholipases A2 (sPLA(2)s), the group X enzyme has the most potent hydrolyzing capacity toward phosphatidylcholine, the major phospholipid of cell membrane and lipoproteins. This enzyme has recently been implicated in chronic inflammatory diseases such as atherosclerosis and asthma and may also play a role in colon tumorigenesis. We show here that group X sPLA(2) [mouse (m)GX] is one of the most highly expressed PLA(2) in the mouse colon and that recombinant mouse and human enzymes stimulate proliferation and mitogen-activated protein kinase activation of various colon cell lines, including Colon-26 cancer cells. Among various recombinant sPLA(2)s, mGX is the most potent enzyme to stimulate cell proliferation. Based on the use of sPLA(2) inhibitors, catalytic site mutants, and small interfering RNA silencing of cytosolic PLA(2)alpha and M-type sPLA(2) receptor, we demonstrate that mGX promotes cell proliferation independently of the receptor and via its intrinsic catalytic activity and production of free arachidonic acid and lysophospholipids, which are mitogenic by themselves. mGX can also elicit the production of large amounts of prostaglandin E2 and other eicosanoids from Colon-26 cells, but these lipid mediators do not play a role in mGX-induced cell proliferation because inhibitors of cyclooxygenases and lipoxygenases do not prevent sPLA(2) mitogenic effects. Together, our results indicate that group X sPLA(2) may play an important role in colon tumorigenesis by promoting cancer cell proliferation and releasing various lipid mediators involved in other key events in cancer progression.
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PMID:Group X phospholipase A2 stimulates the proliferation of colon cancer cells by producing various lipid mediators. 1960 73