Friday, May 10, 2013

GENETIC DISTURBANCES IN OVARIAN CANCERS! ANOTHER CASE OF RECEPTOR FAILURE

In many triple negative Breast Cancers, we have submitted that a failure of the receptor for either HER-2 or ER are the origin. Defective Heparan surface may be one example leading to Receptor ineffective performance.  There is a secondary over production of Tumor Growth factor which impact other Receptors which are naturally susceptible leading to hyperplasia and eventually to a neoplastic process.

In ovarian cancer, the findings that the DAB2 gene is suppressed appears to be central to the pathophysiology of this cancer.
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DAB2

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Dab, mitogen-responsive phosphoprotein, homolog 2 (Drosophila)

PDB rendering based on 1m7e.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols DAB2; DOC-2; DOC2
External IDs OMIM601236 MGI109175 HomoloGene1026 GeneCards: DAB2 Gene
RNA expression pattern
PBB GE DAB2 201278 at tn.png
PBB GE DAB2 201279 s at tn.png
PBB GE DAB2 201280 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 1601 13132
Ensembl ENSG00000153071 ENSMUSG00000022150
UniProt P98082 P98078
RefSeq (mRNA) NM_001244871 NM_001008702
RefSeq (protein) NP_001231800 NP_001008702
Location (UCSC) Chr 5:
39.37 – 39.46 Mb
Chr 15:
6.3 – 6.44 Mb

PubMed search [1] [2]
Disabled homolog 2 is a protein that in humans is encoded by the DAB2 gene.[1][2]
DAB2 mRNA is expressed in normal ovarian epithelial cells but is down-regulated or absent from ovarian carcinoma cell lines. The 770-amino acid predicted protein has an overall 83% identity with the mouse p96 protein, a putative mitogen-responsive phosphoprotein;=============================================================

IF YOU FOLLOW THE MONEY FOR A WHILE YOU WILL COME TO THE NATURAL CONCLUSION.  OVARIAN CANCERS HAPPEN IN MOTHERS! AND GUESS WHO DAB2 GENE WILL PICK ON, OF COURSE A GENE CALLED "MOTHER".

Mothers against decapentaplegic homolog 3

From Wikipedia, the free encyclopedia
.
Mothers against decapentaplegic homolog 3 also known as SMAD family member 3 or SMAD3 is a protein that in humans is encoded by the SMAD3 gene.[1][2] SMAD3 is a member of the SMAD family of proteins.
The human SMAD3 gene is located on chromosome 15. It is one of several human homologues of a gene that was originally discovered in the fruit fly Drosophila melanogaster.


Activin and inhibin are two closely related protein complexes that have almost directly opposite biological effects. Activin enhances FSH biosynthesis and secretion, and participates in the regulation of the menstrual cycle. Many other functions have been found to be exerted by activin, including roles in cell proliferation, differentiation, apoptosis,[1] metabolism, homeostasis, immune response, wound repair,[2] and endocrine function. Conversely inhibin downregulates FSH synthesis and inhibits FSH secretion.[3]
Activin is a dimer composed of two identical or very similar beta subunits. Inhibin is also a dimer wherein the first component is a beta subunit similar or identical to the beta subunit in activin. However, in contrast to activin, the second component of the inhibin dimer is a more distantly-related alpha subunit.[4][5] Activin, inhibin and a number of other structurally related proteins such as anti-Müllerian hormone, bone morphogenetic protein, and growth differentiation factor belong to the TGF-β protein superfamily.[6]

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SO CLEARLY DEPRESSION AT DAB2 WILL INDUCE DE-SENSITIZATION AT THE TGF-BETA RECEPTOR LEADING TO CHANGES OR MODULATION THAT FAVOR ACTIVIN'S ACTIVITY AND PROLIFERATION

BUT DEPRESSION OF DAB2 DOES NOT STOP THERE, THROUGH ITS GIPC1 CONNECTION IT WILL AFFECT VERY BAD ACTORS INCLUDING MYO6 (WHICH DISTURBS ORGANELLE MOVEMENT AND VACUOLE CONTROL TRAFFIC IN THE CELL) AND LPR1,2 A DISFIGURING GENE ASSOCIATED WITH A BAD SYNDROME AND THE "DEVIL" DVL3.  AND REMEMBER A GENE THAT INDUCES MORPHOLOGIC DISTURBANCE SUCH AS THE LRP2 IS DANGEROUS TO DANCE WITH!   ALWAYS REMEMBER THALIDOMIDE WITH ITS SHORT LIMB SYNDROME!
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 Mutations in the LRP2 gene are associated with Donnai-Barrow syndrome.[6]


This disorder is characterized by unusual facial features, including prominent, wide-set eyes with outer corners that point downward; a short bulbous nose with a flat nasal bridge; ears that are rotated backward; and a widow's peak hairline.
Individuals with Donnai-Barrow syndrome have severe hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss). In addition, they often experience vision problems, including extreme nearsightedness (high myopia), detachment or deterioration of the light-sensitive tissue in the back of the eye (the retina), and progressive vision loss. Some have a gap or split in the colored part of the eye (iris coloboma).[2][3]
In almost all people with Donnai-Barrow syndrome, the tissue connecting the left and right halves of the brain (corpus callosum) is underdeveloped or absent. Affected individuals may also have other structural abnormalities of the brain. They generally have mild to moderate intellectual disability and developmental delay.
People with Donnai-Barrow syndrome may also have a hole in the muscle that separates the abdomen from the chest cavity (the diaphragm), which is called a diaphragmatic hernia. This potentially serious birth defect allows the stomach and intestines to move into the chest and possibly crowd the developing heart and lungs. An opening in the wall of the abdomen (an omphalocele) that allows the abdominal organs to protrude through the navel may also occur in affected individuals. Occasionally people with Donnai-Barrow syndrome have abnormalities of the intestine, heart, or other organs and scoliosis.[2][3]

MYO6

From Wikipedia, the free encyclopedia
.
Myosin VI, also known as MYO6, is a protein. It has been found in humans, mice, fruit flies (Drosophila melanogaster), and nematodes (Caenorhabditis elegans).
Myosin VI is a molecular motor involved in intracellular vesicle and organelle transport. It is one of the so-called unconventional myosins.[supplied by OMIM][1]

Interactions

MYO6 has been shown to interact with GIPC1[2][3] and DAB2.[4][5]
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CAN THIS ENTIRE MACHINERY BE SHUT DOWN BY AN ANTI-CD81
I BET YOU! 

THE CENTRAL GENE TO GO AFTER IS GIPC1 FROM MY VOTE, THERE IS THE CROSS-ROAD!  BUT IT INVOLVES THE ADRENAL RECEPTORS AND BETA RECEPTOR OF THE HEART SO CARDIAC MONITOR WOULD BE ADVISED DURING PHASE 1 STUDIES!

If LPR2 is amplified, will that predict activity of Avastin and other immunomodulation?  we know that when morphology is involved, these agents are active!
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