As we look for the cure, we aim at specific genes as target for our therapy
The challenges are multiple
1-which gene to take up
2-which receptor or cluster of differentiation (CD) to block
3.which pathway to tone down or amplify
while it appears that blocking is evidently easier achieved, amplifying a gene continue to pose a challenge in vivo. It requires knowing some of the normal inhibitor (s) (or regulator) to the gene, finding a promoter gene or globally amplify the genome such as done by c-MYC.
ONE GENE WE HAVE NOT TALKED ABOUT ENOUGH I BELIEVE IS THE CTNNB1
WE TEND TO ONLY LOOK AT ITS ROLE AS AN ADHESION MOLECULE AND THEREFORE IMPORTANT ONLY IN THE METASTATIC PROCESS, IN FACT IT IS THE DOOR TO THE Wnt AND ENDO/MESODERMAL TRANSFORMATION.
JUST LOOKAT WHAT IS SAID ABOUT IT!
|"CTNNB1 a regulator of cell adhesion and a key downstream effector in the Wnt signaling pathway. Implicated early embryonic development and tumorigenesis. Phosphorylated and destabilized by CK1 and GSK-3beta. Stabilized cytoplasmic beta-catenin is a hallmark of a variety of cancers. Stabilized beta-catenin translocates to the nucleus, where it acts as a transcriptional activator of T-cell factor (TCF)-regulated genes. Interacts with the PDZ domain of TAX1BP3, inhibiting its transcriptional activity. Two alternatively spliced human isoforms have been described. Note: This description may include information from UniProtKB.|
|Protein type: Actin binding protein; Nuclear receptor co-regulator; Motility/polarity/chemotaxis; Cell adhesion; Transcription factor|
|Cellular Component: desmosome; centrosome; basolateral plasma membrane; fascia adherens; intercellular junction; zonula adherens; cytosol; beta-catenin destruction complex; transcription factor complex; cell-cell adherens junction; membrane; lamellipodium; perinuclear region of cytoplasm; cytoplasm; synapse; dendritic shaft; lateral plasma membrane; spindle pole; internal side of plasma membrane; catenin complex; cell cortex; Z disc; cell-substrate adherens junction; adherens junction; microvillus membrane; apical part of cell; plasma membrane; nucleus; cell junction|
|Molecular Function: protein C-terminus binding; identical protein binding; transcription coactivator activity; protein phosphatase binding; transcription factor binding; protein kinase binding; ionotropic glutamate receptor binding; signal transducer activity; protein binding; enzyme binding; androgen receptor binding; cadherin binding; double-stranded DNA binding; estrogen receptor binding; chromatin binding; SMAD binding; structural molecule activity; kinase binding; transcription factor activity; alpha-catenin binding; nuclear hormone receptor binding|
|Biological Process: skin development; regulation of myelination; regulation of centriole-centriole cohesion; positive regulation of apoptosis; positive regulation of transcription, DNA-dependent; regulation of fibroblast proliferation; negative regulation of chondrocyte differentiation; cell maturation; T cell differentiation in the thymus; positive regulation of fibroblast growth factor receptor signaling pathway; Wnt receptor signaling pathway through beta-catenin; osteoclast differentiation; cell-cell adhesion; positive regulation of endothelial cell differentiation; positive regulation of mesenchymal cell proliferation; embryonic foregut morphogenesis; male genitalia development; synapse organization and biogenesis; ectoderm development; cell adhesion; embryonic limb morphogenesis; hindbrain development; bone resorption; response to drug; positive regulation of neuroblast proliferation; tongue morphogenesis; positive regulation of I-kappaB kinase/NF-kappaB cascade; regulation of smooth muscle cell proliferation; transcription, DNA-dependent; hair cell differentiation; genitalia morphogenesis; patterning of blood vessels; muscle cell differentiation; midgut development; smooth muscle cell differentiation; positive regulation of transcription from RNA polymerase II promoter; embryonic digit morphogenesis; negative regulation of transcription, DNA-dependent; oocyte development; negative regulation of apoptosis; negative regulation of osteoclast differentiation; glial cell fate determination; endodermal cell fate commitment; apoptosis; cell-matrix adhesion; neuron migration; dorsal/ventral axis specification; cell fate specification; determination of dorsoventral asymmetry; negative regulation of transcription from RNA polymerase II promoter; embryonic hindlimb morphogenesis; response to estradiol stimulus; negative regulation of cell proliferation; central nervous system vasculogenesis; positive regulation of MAPKKK cascade; pancreas development; forebrain development; fallopian tube development; proximal/distal pattern formation; cell structure disassembly during apoptosis; Wnt receptor signaling pathway; hair follicle morphogenesis; thymus development; in utero embryonic development; cytoskeletal anchoring; embryonic axis specification; regulation of T cell proliferation; synaptic vesicle transport; gastrulation with mouth forming second; liver development; regulation of angiogenesis; odontogenesis of dentine-containing teeth; negative regulation of oligodendrocyte differentiation; myoblast differentiation; positive regulation of osteoblast differentiation; Schwann cell proliferation; response to cadmium ion; ureteric bud branching; response to cytokine stimulus; androgen receptor signaling pathway; positive regulation of muscle cell differentiation; epithelial to mesenchymal transition; embryonic heart tube development; lens morphogenesis in camera-type eye; anterior/posterior axis specification|
HOW DO YOU AMPLIFY A GENE YOU WANT AMPLIFIED IN VIVO
CASE IN POINT THE FHIT GENE
ONE OF THE REASON CANCER MUTATES THIS GENE IN A HURRY IS BECAUSE IT WANT TO REMOVE ITS REPRESSION ON HER-2 DRIVEN EVENTS, AND CONTROL OVER THE BRCA (s). RESTORING ITS FUNCTION IS A CRITICAL ACTIVITY AND WILL GO ALONG WAY TO IMPROVE THE SITUATION IN MANY CANCER AND MOST IMPORTANTLY LUNG CANCER! THE NUMBER ONE KILLER CANCER. THIS IS WHY THE DRUG RESTORING P53 IS BEING OF PRIMARY INTEREST AS SUGGESTED IN OUR PREVIOUS BLOG. RESTORING THE FUNCTIONS OF A SUPPRESSOR GENE THAT HAS BEEN MUTATED WOULD BE A FEAST IN SOME CANCERS AND A CRITICAL CORRECTION IN SOME OTHERS!