Thursday, January 31, 2013

CELLULAR LANGUAGE

The challenge brought to us by the need of a cure and failure of destructive conventional chemotherapy have proven to human being that there is the need to understand better cellular function.  Our learning has led to discover that the Cell has many properties and can do many things on its own including dying on its own or cell programmed death.  Yes, coordinated Changes within the cell based on its age, position and state of independence or loss of input from other cell can trigger cell death.  These coordinated changes are indeed a language that one   must talk to send a message to the cell that it is time to die.  And it is now apparent to scientists that brutalizing and violence to a cell through chemotherapy and Radiation will never be sufficient to accomplish a cure.  Cells are ready for a violent attack. You need to convince the cell to die.  You need to target functions of the cell and already tough to conquer cancer start listening.  By targeting therapy we learn that cutting a signal could lead to death of a cell.  like a battery, there is a positive and negative.  in the cell, there switches which are on or off.  In a computer there 1 and zero.  What a computer can do with these 1 basic things is anybodies guess. The Morse language had only 2 signal Tic and Tan.  (Tic Tan Tic, Tan TAN tic!)
Through an ON and OFF switch, through a positive and negative electrical charge, the cell transfer an input that will lead to extensive result.
While empirically we tend to believe that more is better,  it it the OFF signal that is the most full off consequences.

AT CELLULAR LEVEL, LACK OF INPUT IS THE MOST FULL OF CONSEQUENCE AND CAN LEAD TO DEATH IF SPOKEN AT THE RIGHT PLACE AND THE RIGHT TIME.

1. If a cell is left alone.  lack of environment talking to it (ie.  IN MYELOMA), lack of sister cell talking to it, lack of positive excitatory stimulation, will kill it . We have called this ANOIKIS.

2.Target Therapy works because it BLOCKS the excitatory stimulation.

3. A post synaptic neuron will die if the pre-synaptic neuron stops sending excitatory input.

4. Muscle death or Atrophy will occur if synaptic input cease or desist.
5. Necrosis will occur if Oxygen ceases
6. Acid from Lysosome will kill the cell if it seeps in the Cytosol that is relatively basic

BASICALLY, IT 'S AGAIN IT'S ON OR OFF, TIC OR TAN, NEGATIVE POSITIVE, ONE OR ZERO EVEN AT CELLULAR LEVEL.

IF YOU GET THIS, THE YOU WILL ALSO UNDERSTAND THAT
AT GENE LEVEL, IT IS THE DECREASE OF GENE THAT IS MORE IMPORTANT THEN AMPLIFICATION

1. Suppression of PTEN in sarcoma or lung cancer will act on PI3K/MTOR
2. decrease or suppression of STAT1 will be present in triple negative Breast cancer
3. P53 silencing mutation
4. MDM2 silencing Mutation
5. gene deletion or silencing
6.
Oncogene. 2005 Sep 15;24(41):6269-80.

The polycomb group protein enhancer of zeste homolog 2 (EZH 2) is an oncogene that influences myeloma cell growth and the mutant ras phenotype.

Source

The Graduate Program in Molecular, Cellular, Developmental Biology, and Genetics, University of Minnesota, Minneapolis, MN 55455, USA.

Abstract

Three distinct proliferative signals for multiple myeloma (MM) cell lines induce enhancer of zeste homolog 2 (ezh 2) transcript expression. EZH 2 is a polycomb group protein that mediates repression of gene transcription at the chromatin level through its methyltransferase activity. Normal bone marrow plasma cells do not express ezh2; however, gene expression is induced and correlates with tumor burden during progression of this disease. We therefore investigated how EZH 2 expression is deregulated in MM cell lines and determined the consequence of this activity on proliferation and transformation. We found that EZH 2 protein expression is induced by interleukin 6 (IL-6) in growth factor-dependent cell lines and is constitutive in IL-6-independent cell lines. Furthermore, EZH 2 expression correlates with proliferation and B-cell terminal differentiation. Significantly, EZH 2 protein inhibition by short interference RNA treatment results in MM cell growth arrest. Conversely, EZH 2 ectopic overexpression induces growth factor independence. We found that the growth factor-independent proliferative phenotype in MM cell lines harboring a mutant N- or K-ras gene requires EZH 2 activity. Finally, this is the first report to demonstrate that EZH 2 has oncogenic activity in vivo, and that cell transformation and tumor formation require histone methyltransferase activity.
Oncogene (2005) 24, 6269-6280.

7.NME1/NM23


NME1

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NME/NM23 nucleoside diphosphate kinase 1

PDB rendering based on 1be4.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols NME1; AWD; GAAD; NB; NBS; NDKA; NDPK-A; NDPKA; NM23; NM23-H1
External IDs OMIM156490 MGI97355 HomoloGene128514 ChEMBL: 2159 GeneCards: NME1 Gene
EC number 2.7.4.6
Orthologs
Species Human Mouse
Entrez 4830 18102
Ensembl ENSG00000239672 ENSMUSG00000037601
UniProt P15531 P15532
RefSeq (mRNA) NM_000269.2 NM_008704.2
RefSeq (protein) NP_000260.1 NP_032730.1
Location (UCSC) Chr 17:
49.23 – 49.24 Mb
Chr 11:
93.96 – 93.97 Mb

PubMed search [1] [2]
Nucleoside diphosphate kinase A is an enzyme that in humans is encoded by the NME1 gene.[1] It is thought to be a metastasis suppressor.
This gene (NME1) was identified because of its reduced mRNA transcript levels in highly metastatic cells. Nucleoside diphosphate kinase (NDK) exists as a hexamer composed of 'A' (encoded by this gene) and 'B' (encoded by NME2) isoforms. Mutations in this gene have been identified in aggressive neuroblastomas. Two transcript variants encoding different isoforms have been found for this gene. Co-transcription of this gene and the neighboring downstream gene (NME2) generates naturally-occurring transcripts (NME1-NME2), which encodes a fusion protein consisting of sequence sharing identity with each individual gene product.[2]


Interactions

NME1 has been shown to interact with Aurora A kinase,[3] NME3,[4][5] Protein SET,[6] RAR-related orphan receptor alpha,[7] TERF1,[8] CD29[9] and RAR-related orphan receptor beta.[7]


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8 IN SARCOMA, DELETION OF CDKN2A 
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9. DECREASE IN E-CADHERIN IN  METASTATIC DISEASE
AND EARLY TRANSFORMATION
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AND THE LIST OF TUMOR SUPPRESSION GENE GOES ON.

SO IN GENERAL CANCER IS CAUSED BY NEGATIVE. LACK OR SUPPRESSION OF A GENE
SO ANYTIME THAT YOU ARE LOOKING FOR CAUSE OF CANCER, PAY MORE ATTENTION TO THE SUPPRESSION NOT THE HYPERACTIVITY!
LET SUPPRESS  FOXO3 TO TELL CANCER TO DIE!  LET'S CONTINUE TO SUPPRESS GROWTH FACTORSAND THE CURE WILL BE OUR TO REACH!
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