Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:O76050 (neu)
 3,969 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Overexpression of the epithelial specific matrix metalloproteinase matrilysin (MAT) has been correlated with enhanced tumorigenicity and tumor cell invasion using in vitro model systems. We have determined the effects of MAT expression on the development of mammary tumorigenesis using transgenic mice that express human MAT under the control of the mouse mammary tumor virus (MMTV)-long terminal repeat promoter/enhancer. Examination of mammary glands from multiparous MMTV-MAT animals revealed the development of premalignant hyperplastic alveolar nodules in 50% of aged females. MMTV-MAT mice were mated with MMTV-neu transgenic mice to determine the effect of MAT on neu-induced mammary tumorigenesis. Bigenic MMTV-MAT/neu female offspring developed primary mammary tumors approximately 13 weeks earlier than did MMTV-neu controls. The mechanism of enhanced neu-induced tumorigenesis was explored. No discernible difference in Neu receptor dimerization or activation was detected in MMTV-MAT/neu tumors or mammary glands compared to MMTV-neu controls. A similar percentage of MMTV-MAT/neu and MMTV-neu tumors acquired deletions in the neu transgene, which have previously been shown to result in constitutive receptor activation. The presence of premalignant nodules and the accelerated development of oncogene-induced mammary tumors suggest that expression of MAT in the mammary epithelium contributes to early-stage mammary tumorigenesis.
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PMID:The matrix metalloproteinase matrilysin influences early-stage mammary tumorigenesis. 985 86

Low oxygen tension (hypoxia) has been implicated in proliferation of vascular smooth muscle cells (SMCs) of the lung. Tissue hypoxia also occurs in the obstructed bladder. The extracellular-regulated kinase mitogen-activated protein kinase 1/2 (Erk1/2) pathway is induced in many cell types during hypoxia. We examined whether hypoxia (3% O2), compared with normoxia (21% O2), induces proliferation responses and activation of the Erk1/2 pathways in primary rat bladder smooth muscle cells (BSMCs). We show that hypoxia induces proliferation of BSMCs at 18 h and, although reduced at 22 h, still remained above normoxic levels. Hypoxia induced a strikingly transient activation of Erk1/2 that lasted only 10-30 min. However, inhibition of the transient Erk1/2 activity with a specific mitogen-activated protein kinase kinase 1 (MEK-1) inhibitor PD 98059 prevented subsequent hypoxia-induced proliferation at 18 h. Interestingly, inhibition of general matrix metalloproteinase (MMP) activity, using either doxycycline or GM 6001, prevented both transient Erk1/2 activity and subsequent proliferation in response to hypoxia. Furthermore, MMP-7 (matrilysin) is activated in the conditioned medium (CM) of BSMCs at 10-20 min of hypoxia. In addition, MMP-7 was also transcriptionally induced at 6 h of hypoxia in an Erk1/2-dependent manner. Moreover, transient Erk1/2 activation and BSMC proliferation were both dependent on epidermal growth factor receptor (EGFR/HER1) but not neu receptor (HER2/ERB2) autophosphorylation. We conclude that hypoxia leads to Erk1/2 activation, which appears to modulate BSMC proliferation through MMP-7-and EGFR-mediated mechanisms.
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PMID:Matrix metalloproteinase-7 and epidermal growth factor receptor mediate hypoxia-induced extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase activation and subsequent proliferation in bladder smooth muscle cells. 1684 31