Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20645 (mannose-6-phosphate receptor)
 320 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied estrogen-regulated proteins in an attempt to understand the mechanism by which estrogens stimulate cell proliferation and mammary carcinogenesis. In estrogen receptor positive human breast cancer cell lines (MCF7, ZR75-1) estrogens specifically increase the production into the culture medium of a 52,000 daltons (52K) glycoprotein. Several high affinity monoclonal antibodies to the partially purified secretory 52K protein have allowed to purify to homogeneity this protein and its cellular processed products. The 52K protein has been identified as the secreted precursor of a cathepsin-D like protease bearing mannose-6-phosphate signals and routed to lysosomes via mannose-6-phosphate receptor. The protease is mitogenic in vitro on estrogen deprived MCF7 cells and is able to degrade basement membrane and proteoglycans following its activation. The cellular related proteins, as detected by immunohistochemistry and immunoassay are more concentrated in proliferative mammary ducts than in resting ducts and their concentration in breast cancer cytosol appears to be more correlated with lymph nodes invasion and disease free survival (with S. Thorpe, Copenhagen) than with the estrogen receptor (RE) level. The protein is also produced constitutively by RE-negative cell lines, while in some antiestrogen resistant variants, it becomes inducible by tamoxifen, contrary to the wild type MCF7 cells. Cloning of its cDNA in lambda gt11 has allowed to show that the mRNA is rapidly induced by estrogens and to sequence the protein and compare it to that of the normal human kidney cathepsin-D.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The estrogen-regulated 52K-cathepsin-D in breast cancer: from biology to clinical applications. 365 55

Liver enlargement is a common feature of non-genotoxic rodent hepatocarcinogens administered at high doses. In the present study, the expression of growth factors and growth factor receptors was investigated in the C57BL/1OJ mouse during liver enlargement induced by the non-genotoxic rodent hepatocarcinogen, sodium phenobarbitone (PB). Male mice were dosed 0-2500 p.p.m. PB in the diet for 1, 4 and 13 weeks. There was a dose and time dependent increase in liver weight. Hepatocyte replication, assessed by incorporation of bromodeoxyuridine, was increased in a dose-dependent manner at week 1 only (18-fold increase at 2000 p.p.m.) and was predominantly localized in the centrilobular region. At week 1, PB (2500 p.p.m.) caused transient increases in transforming growth factor alpha (TGFalpha) and epidermal growth factor receptor (EGFR) and decreases in transforming growth factor beta1 (TGF-beta1) and mannose-6-phosphate receptor (M6PR) in centrilobular hepatocytes which correlated with the replication in this region. At week 1, there was an increase in both hepatocyte growth factor (HGF) and hepatocyte growth factor receptor (HGFR) which colocalized in centrilobular hepatocytes; in some mice or periportal hepatocytes in other mice. After 13 weeks, HGF and HGFR were localized in the cytoplasm of centrilobular hepatocytes of all mice but exhibited a differential intracellular distribution across the lobule. At 2500 p.p.m. PB, EGFR and HGFR mRNA were essentially unchanged over the 13 week dosing period whilst M6PR mRNA was increased 2- to 4-fold. At 2500 p.p.m. PB, EGFR protein levels from immunoblots showed a consistent decrease over the 13 weeks whilst M6PR and HGFR protein levels were essentially unchanged. The protein level and mRNA data for EGFR suggest post-transcriptional modification. Thus, phenobarbitone caused transient replication of hepatocytes and modulation of growth stimulatory and inhibitory factors and their associated receptors in terms of overall levels and regional distribution in the liver.
Carcinogenesis 1996 May
PMID:Expression of growth factors and growth factor receptors in the liver of C57BL/10J mice following administration of phenobarbitone. 864 Sep 46

The insulin-like growth factor II/mannose-6-phosphate receptor (IGF2R) mediates trafficking of mannose-6-phosphate (M6P)-containing proteins and the mitogenic hormone IGF2. IGF2R also plays an important role as a tumor suppressor, as mutation is frequently associated with human carcinogenesis. IGF2 binds to domain 11, one of 15 extracellular domains on IGF2R. The crystal structure of domain 11 and the solution structure of IGF2 have been reported, but, to date, there has been limited success when using crystallography to study the interaction of IGFs with their binding partners. As an approach to investigate the interaction between IGF2 and IGF2R, we have used heteronuclear NMR in combination with existing mutagenesis data to derive models of the domain 11-IGF2 complex by using the program HADDOCK. The models reveal that the molecular interaction is driven by critical hydrophobic residues on IGF2 and IGF2R, while a ring of flexible, charged residues on IGF2R may modulate binding.
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PMID:Structural insights into the interaction of insulin-like growth factor 2 with IGF2R domain 11. 1785 Jul 46