SOME LITTLE GENES WITH A BIG IDEA: SHP GENE

IF YOU KNOW HOW IMPORTANT ESTROGEN RECEPTORS ARE IN BREAST CANCERS,
IF YOU KNOW HOW IMPORTANT ANDROGEN RECEPTORS ARE IN PROSTATE CANCER
IF YOU REALIZE HOW IMPORTANT THE THYROID FUNCTION IS DRIVING THE RATE OF METABOLISM
IF YOU REALIZE THE DIFFICULTY THAT POSES HEPATOMA IN TERMS OF TREATMENT,
IF YOU KNOW THAT SARCOMA IS TOUGH TO TREAT,

THEN YOU SHOULD DIG DEEPER IN UNDERSTANDING THAT ALL THESE RECEPTORS HAVE ONLY ONE INHIBITOR, THE "SMALL HETERODIMER PARTNER"  GENE!

WHAT IS IT AND HOW AND WHEN SHOULD IT COME IN?

Small heterodimer partner has been shown to interact with:

• Androgen receptor,^[4]
• Estrogen receptor alpha,^[5]
• Hepatocyte nuclear factor 4 alpha,^[6]
• Liver receptor homolog-1,^[7][8]
• Liver X receptor alpha,^[7]
• Peroxisome proliferator-activated receptor gamma,^[9]
• Retinoic acid receptor alpha,^[10][11] and
• Retinoid X receptor alpha.^[6][7]

I refuse to comment on the PPARgamma for now, did you know that this is the staff that interacts with Rb1?  watch it as it is coming to a Diabetic control and evaluation near you!

At CRBCM we are working hard!

Processes of cancerization

One of the most intriguing steps in the neoplastic transformation is determining the actual event that led to its occurrence. We all have the perception that because of what we ingest unfortunately on a continuous basis (medications or foods we like - man clings to habits) something will get either amplified or suppressed.  Certain amplifications can be deleterious or beneficial depending of where they occur or what gene is involved.  It is apparent that involvement of "wild genes" (those with multiple interactions with others, including genes involved in shaping the body) are more likely to lead to malignant transformation (ie. the Androgen gene, FYN,Grb2, MTIF, etc).  Secondly, knocking out break to proliferation (P53, Rb1, PTEN, and the many CDK) seems also to be a prelude to a neoplastic transformation.   Alteration in "switch" genes (SOS) and molecules intermediary to various cellular/membrane events can also trigger a persistent stimulation or suppression that could affect cellular processes enough to upset a balance.  Chronic hypoxia has emerged to be a potent neoplastic process inducer....(to be continued)

Esophageal Cancer (continued)

We have discussed that chemical, traumatic and sometimes burns from caustic solutions that people ingest unfortunately, that will stimulate the cellular membrane receptors which in turn will stimulate RAS, which in turn will amplify PI3K, MAP Kinase and RAL/CDC42.   But remember these are stressful stimulations, so instead of the standard MAPK, the stimulation is imposing on RAS to awake the NFkB pathway, the c_JUN and at nuclear level the FOS which results in inflammatory proteins stimulation including cyclin production or liberation from membranes with extracellular release of Metalloproteases. Cyclins combining to CDCs will exacerbate cell divisions and proliferation, growth factors will promote cell growth, there is an associated ligase proliferation that will impact P53 (through MDM2) and  c-MYC, NOTCH, and even c_JUN itself through FBW7/hCDC4.  This is how the proteasomes come into play!

By now you now
1. that amplification of c-MYC exacerbate proliferation by allowing progression of cells int S-phase and bolster DNA replication, imparting bad prognosis to cancer cells.
(nature is kind and gies you a chance to affect here by freeing RB1 and increasing FBW7.  Oh! also find MYCN and the p isoform to q for answers!)

2 Rb1 does sequester E2F.   you can look at it both ways.  that E2F stabilize Rb1 instead,  whichever way one stop the other for acting!   Remember E2F activates CPP32 which increase APOPTOSIS!  (DRUM UP THOSE TARGET THERAPY!)

3.REMEMBER RAS NEEDS A FATTY ACID MOIETY TO STAY AT THE MEMBRANE FOR ITS ACTIVITY (THIS IS ITS SO CALLED POST-TRANSLATIONAL MODIFICATION) BY THIS PHRENYLATION IS IMPAIRED BY THE FARNESYL TRANSFERASE INHIBITOR
(ie. TIPIFARNIB) THAT WE DO NOT USE ENOUGH I FEEL!  ALTHOUGH I AGREE THAT SIDE EFFECTS MAY BE PROHIBITIVE GIVEN THE EXTENT OF WHICH NORMAL CELLS WILL ALSO BE COMPROMISED.  BUT IT GOES TO THE FACT THAT WE NEED TO FURTHER TWEAK THIS MODALITY TO MAKE IT USABLE IN CANCERS!
ANTI-MEK HAVE DEMONSTRATED USE IN KRAS MUTATION CANCERS!  MAY BE ESOPHAGEAL CANCERS WILL BENEFIT HERE!

4Role of combining Velcade and Carfilzomib in Esophageal cancer to see if c-Myc can be affected?   Will it increase the right Ligand (FBW7)?