Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Overexpression of the HER2 (neu/c-erbB-2) oncogene frequently coincides with an aggressive clinical course of certain human adenocarcinomas. Expression and secretion of aberrant HER2 splice variants has been reported in various cell lines and tissues and can interfere with the oncogenic HER2 activity. Here we demonstrate, using two different approaches, that expression of a truncated 100 kDa HER2 variant which encodes the extracellular domain of HER2 (HER-ECD) inhibits growth factor-mediated tumour cell proliferation. A HER2-ECD cDNA encoding the truncated variant was overexpressed in MCF7 breast cancer cells. HER2-ECD overexpression decreased spontaneous proliferation of MCF7 cells as well as heregulin-mediated soft agar colony formation. Concomitantly, heregulin-induced phosphorylation of HER4 as well as downstream activation of p44/p42 MAP-kinases was decreased. To confirm these data, ribozymes were targeted to the 3'-untranslated region of the 2.3 kb HER2-ECD mRNA which is spontaneously expressed in MKN7 gastric cancer cells. HER2-ECD-targeted ribozymes downregulated HER2-ECD expression and enhanced EGF-mediated soft agar colony formation of MKN7 cells. In parallel, EGF-induced activation of p44/p42 MAP-kinases and activation of c-Fos expression were increased in ribozyme-transfected MKN7 cells. Finally, in RT-PCR we found a trend towards a progressive loss of 2.3 kb HER2-ECD mRNA expression in more advanced gastric tumours. These data show that the HER2-ECD variant inhibits growth factor-mediated tumour cell proliferation suggesting an important role during the progression of human cancer.
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PMID:Expression of a truncated 100 kDa HER2 splice variant acts as an endogenous inhibitor of tumour cell proliferation. 1136 Jan 94

Osteosarcoma (OS) is the most common primary aggressive and malignant bone tumor. Newly diagnostic OS patients benefit from the standard therapy including surgical resection plus radiotherapy and neoadjuvant chemotherapy (MAP chemotherapy: high-dose methotrexate, doxorubicin and cisplatin). However, tumor recurrence and metastasis give rise to a sharp decline of the 5-year overall survival rate in OS patients. Little improvement has been made for decades, urging the development of more effective therapeutic approaches. ErbB receptor family including EGFR, HER2, HER3 and HER4, being important to the activation of PI3K/Akt and MAPK signaling pathways, are potential targets for OS treatment. Genetic aberrations (amplification, overexpression, mutation and altered splicing) of ErbB are essential to the growth, apoptosis, motility and metastasis in a variety of cancers. Overexpression of ErbB family is associated with the poor prognosis of cancer patients. A number of monoclonal antibodies or inhibitors specific for ErbB family have entered clinical trials in a range of solid tumors including breast carcinoma, lung carcinoma and sarcoma. Here, we summarized the roles and expression of ErbB family in OS and the current development of ErbB-targeted therapeutic strategies including chemotherapies and immunotherapies for OS treatment.
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PMID:Advanced development of ErbB family-targeted therapies in osteosarcoma treatment. 3035 45