Showing posts with label exostosis. Show all posts
Showing posts with label exostosis. Show all posts

Saturday, April 20, 2013

TRIPLE NEGATIVE BREAST CANCER WITH BASAL CELL LIKE CANCER CELLS

Are you kidding me or just fooling me?
Could patients having this disease also have a Glycosylation problem?
Are they suffering from a form of Hereditary Multiple exostosis?
Do they have EXT gene Mutation?
 By claiming the following:
"The mechanism of HME pathology is likely rooted in a disruption of the normal distribution of HS-binding growth factors, which include FGF and morphogens such as hedgehog, Wnt, and members of the TGF-β family. The loss of HS disrupts these pathways"

Hudson Freeze et al are reporting all the mechanisms involved in Basal cell  breast cancer in one sentence and pin it down to Heparan surface.  He is putting the disruption square and round in the Golgy Apparatus.

It makes perfect sense though, these diseases are triple negative pointing to an insensitive receptor
and sure enough we know that receptors are proteins, but in order to work, proteins need Glycosylation and Heparan Sulfate is  :

"Heparan sulfate /hep·a·ran sul·fate/ (hep´ah-ran) is a glycosaminoglycan occurring in the cell membrane of most cells, consisting of a repeating disaccharide unit of glucosamine and uronic acid residues, which may be acetylated and sulfated; it accumulates in several mucopolysaccharidoses."(wikipedia)

Lack of Glycosylation will render receptor insensitive!

THIS IS THE FULL TEXT OF THEIR CLAIM:
Congenital Exostosis
Defects in the formation of heparan sulfate (HS) cause hereditary multiple exostosis (HME), an autosomal dominant disease with a prevalence of about 1:50,000. It is caused by mutations in two genes EXT1 and EXT2, which are involved in HS synthesis. HME patients have bony outgrowths, usually at the growth plates of the long bones. Normally, the growth plate contains chondrocytes in various stages of development, which are enmeshed in an ordered matrix composed of collagen-chondroitin sulfate. In HME, however, the outgrowths are often capped by disorganized cartilagenous masses with chrondrocytes in different stages of development. About 1–2% of patients also develop osteosarcoma.
HME mutations occur in EXT1 (60–70%) and EXT2 (30–40%). The proteins encoded by these genes are thought to exist as a complex in the Golgi and both are required for polymerizing GlcNAcα1–4 and GlcAβ1–3 into HS. However, the partial loss of one allele of either gene appears sufficient to cause HME. This means that haploinsufficiency decreases the amount of HS and that EXT activity is rate limiting for HS biosynthesis. This is unusual because most glycan biosynthetic enzymes are in substantial excess.
The mechanism of HME pathology is likely rooted in a disruption of the normal distribution of HS-binding growth factors, which include FGF and morphogens such as hedgehog, Wnt, and members of the TGF-β family. The loss of HS disrupts these pathways in Drosophila. Mice that are null for either Ext gene are embryonic lethal and fail to gastrulate; however, Ext heterozygous animals are viable and about one third develop a visible exostoses on the ribs. No exostoses develop on the long bones of these animals (in contrast to patients with HME), but subtle chondrocyte growth abnormalities were seen in the growth plates of these bones. Further studies are needed to understand how truncation of the HS chains leads to ectopic growth plate formation and the phenotype abnormalities.

It becomes urgent to test EXT gene in these patients the TRAP1 gene

TRAP1,
Retinoblastoma protein.[5]

EXT1

From Wikipedia, the free encyclopedia
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Exostosin 1
Identifiers
Symbols EXT1; EXT; LGCR; LGS; TRPS2; TTV
External IDs OMIM608177 MGI894663 HomoloGene30957 GeneCards: EXT1 Gene
EC number 2.4.1.225 2.4.1.224, 2.4.1.225
RNA expression pattern
PBB GE EXT1 201995 at tn.png
PBB GE EXT1 214985 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 2131 14042
Ensembl ENSG00000182197 ENSMUSG00000061731
UniProt Q16394 P97464
RefSeq (mRNA) NM_000127 NM_010162
RefSeq (protein) NP_000118 NP_034292
Location (UCSC) Chr 8:
118.81 – 119.12 Mb
Chr 15:
53.06 – 53.35 Mb

PubMed search [1] [2]
Exostosin-1 is a protein that in humans is encoded by the EXT1 gene.[1]
This gene encodes an endoplasmic reticulum-resident type II transmembrane glycosyltransferase involved in the chain elongation step of heparan sulfate biosynthesis. Mutations in this gene cause the type I form of Multiple Exostoses.[1]
From Wikipedia, the free encyclopedia
Jump to: navigation, search
TNF receptor-associated protein 1
Identifiers
Symbols TRAP1; HSP 75; HSP75; HSP90L; TRAP-1
External IDs OMIM606219 MGI1915265 HomoloGene9457 ChEMBL: 1075132 GeneCards: TRAP1 Gene
RNA expression pattern
PBB GE TRAP1 201391 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 10131 68015
Ensembl ENSG00000126602 ENSMUSG00000005981
UniProt Q12931 Q9CQN1
RefSeq (mRNA) NM_001272049 NM_026508
RefSeq (protein) NP_001258978 NP_080784
Location (UCSC) Chr 16:
3.7 – 3.77 Mb
Chr 16:
4.04 – 4.08 Mb

PubMed search [1] [2]
Heat shock protein 75 kDa, mitochondrial is a protein that in humans is encoded by the TRAP1 gene.[1][2][3]

THESE 4 GENES NEEDS TO BE LOOKED AT ASAP IN TRIPLE NEGATIVE BREAST CANCER WITH BASALOID MORPHOLOGY!