Showing posts with label MUC1. Show all posts
Showing posts with label MUC1. Show all posts

Thursday, August 22, 2013

Example of neoplastic phenomena at work.

One example  of constant  stimulation is an estrogenic supply which leads to type I endometrial cancers. It appears that constantly giving Estrogens unopposed by progestins  leads to the stimulation of many genes including Grb2, a" wild gene" that provokes amplification of critical genes that are controlling the epithelium of the Uterus (Catenins and Muc1) leading to the disturbance of cell polarity and adhesions, events that are preceding hypertrophic transformation.  MUC 1 amplification will shield the cell from immune detection.  How much Sp1, EP 300, and RELA play to further broaden NF-kB amplification in this process remains to be further defined.
RELA is another "wild gene" very much in control of epigenetic phenomena induced by amplification of the NF-kB.
"RELA has been shown to interact with:

Thursday, April 4, 2013

Nomenclature of some Genes in Ovarian Cancer:

Nomenclature of some Genes in Ovarian Cancer:

BRAC1
BRAC2
CDO1
HER-2
CPG ISLAND
TMS1
ER alpha
PRB
MEK
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RASSF1A:  One of the thing cancer cell do is to Methylate some genes in order to block its path to death.
it appears this gene is a critical door to shut or disable.  It not only decrease the significance of RAS and MAPK in the pathogenesis of tumor that harbor this mutation.   It also remove blockage to proliferation by desensitizing the cell to the effect of P53, Cyclins.  Desensititize the cell to Death Receptor 6 and its Fas connection.  RASSF1a, demethylation is a valid target in ovarian cancer
RARbeta
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STRATIFIN.

LAM et al.

 " stratifin, also known as 14-3-3 sigma protein, stimulates matrix metalloproteinase (MMP)-1 expression in dermal fibroblasts.  Treatment of dermal fibroblasts with stratifin resulted in rapid and transient upregulation of c-jun and c-fos mRNA levels.  Stratifin was demonstrated to increase MMP-1 protein levels. Microarray analysis of stratifin-treated fibroblasts shows an increase in Elk4/Sap1 mRNA expression and this finding was confirmed by northern blot analysis. Our results indicate that stratifin markedly increase Elk4/Sap1 mRNA expression in a time-dependent fashion. In conclusion, stratifin stimulates fibroblast MMP-1 levels through the activation of c-fos and MAPK pathway."

Our interpretation is that stratifin is part of an intergrin, its release in the Cytoplasm indeed stimulate MAPK C-JUN and c-fos.  This means it is interpretated by the cell as a chemical stressor. The NF-kB is not far away.  One of the most important hidden information here is the note by the authors that there is an increase of ELK4/Sap1.

ELK4 has been shown to interact with Serum response factor[4][5] and BRCA1.[6]

Serum response factor has been shown to interact with NFYA,[10] Src,[11] CREB-binding protein,[12] GTF2I,[13][14] ATF6,[15] Nuclear receptor co-repressor 2,[16] CEBPB,[17][18] GATA4,[19][20] Myogenin,[21][22] GTF2F1,[23][24] TEAD1,[25] ELK4,[15][26] Promyelocytic leukemia protein[12] and ASCC3.[27]
(wikipedia)

ELK4 therefore control BRCA1 and serum response factor which control NFYA.  This uncover what the cancer cell has to do to start the neoplastic process.  It has to derail genetic repair by abrogating the action of BRAC1, but it also has to take controles of CBF complexes  and NFYA and ZHXY.  Remember CBF complexes control the direction of the metabolism, In essence, when it comes to function in the cell,  the role of Core Binding Factors (CBF) is indistinguishable from that of TRANSCRIPTION FACTORS.  They all impose the direction that the cell metabolism should take.

Remember also that because the Stratifin engages the MAPK mostly through the certain well selected CDK, it will tend to stop cell division.  In Breast cancer, Stratifin is one of the earliest methylated gene slated for silencing.

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HNF1B " Hepatocyte Nuclear Factor 1α (HNF1α) is an atypical homeodomain-containing transcription factor that transactivates liver-specific genes including albumin, α-1-antitrypsin and α- and β-fibrinogen. Biallelic inactivating mutations of HNF1A have been frequently identified in hepatocellular adenomas (HCA), rare benign liver tumors usually developed in women under oral contraceptives, and in rare cases of hepatocellular carcinomas developed in non-cirrhotic liver. HNF1α-mutated HCA (H-HCA) are characterized by a marked steatosis and show activation of glycolysis, lipogenesis, translational machinery and mTOR pathway. We studied the consequences of HNF1α silencing in hepatic cell lines, HepG2 and Hep3B and we reproduced most of the deregulations identified in H-HCA."
 (Laura Pelletier et al)
 This gene is the a gene of differentiation for liver formation, it has the structure of a CBF (core binding Factor) therefore has a subunit binding the DNA therefore silencing that portion, and another subunit having locations for enzymatic proteins or molecular structures that direct assume various functions intended by the cell (formation of Albumin,alpha Antitrypsine, and Beta Fibrinogen)  Interestingly enough, Steatosi is a prominent feature here.  This structure and gene may be of interest in LIPOSARCOMA.?   DOES ACTIVATION OF MTOR DEMONSTRATED HERE OPEN THE DOOR TO USE OF MTOR IN LIPOSARCOMA?
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p16INK4A
p14
CYCLIN D2
SLIT2
CDH13
PTEN
CLAUDIN 3,4
HE4
MUCIN1 OR MUC1
MESOTHELIN
ApoE, J
PIK3CA
P53 AND CHEK2
MLH1
MSH2,6
PMS2
CA-125
STK11
LKB1
PTCH
ATM

This is just the beginning, lets go to work! love those recurring genes as they cross over with presence in other cancers to strengthen their importance, Please remember those that lead to hypothrophy of muscles and extremities are probably more important for therapeutic intervention.  And those with a "q" location on chromosome arm are most likely of poor prognosis or dramatic phenotype expression!  Always do remember that Multidrug resistance (MDR-1) is in play  HERE!

Tuesday, March 26, 2013

A few Genes on Bladder Cancer

MUC1:  Mucinous cancers are known to be dangerous because by the time they are diagnosed, the extent is a little more then first thought.  Mucin is used by cancer cells to hide from immune detection it is believed.  MUC1 interacts with GrB 2 which affects a multitudes of other genes and transcription factors.Through YES1, it interacts with JAK2.  Action through JAK2 may have been why Epogen was prohibited for use in the Curable cancer setting.  JAK2 sensitizes cancer to Epogen, and to other growth factors!
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AZPG1

"Original Article

Oncogene 29, 5146-5158 (16 September 2010) | doi:10.1038/onc.2010.258

AZGP1 is a tumor suppressor in pancreatic cancer inducing mesenchymal-to-epithelial transdifferentiation by inhibiting TGF-β-mediated ERK signaling

B Kong, C W Michalski, X Hong, N Valkovskaya, S Rieder, I Abiatari, S Streit, M Erkan, I Esposito, H Friess and J Kleeff
Epithelial-to-mesenchymal transdifferentiation (EMT) mediated by transforming growth factor-β (TGF-β) signaling leads to aggressive cancer progression. In this study, we identified zinc-α2-glycoprotein (AZGP1, ZAG) as a tumor suppressor in pancreatic ductal adenocarcinoma whose expression is lost due to histone deacetylation."
It is associated with FAT/cahchexic losses in these patients
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TMPRSS2-ERG fusion
NKX3
c-MYC
PTEN
Favorable Gene hCAP-D3
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In Gastric Cancer
LOX
RASSF6
MR1
miRNA 107 (DICER1)
PDCD4
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In Colon Cancer

Annexin
S100A4
SERCA
GF15
BAX