Tuesday, May 21, 2013

THE PROOF IS IN THE PUDDING, WE HYPOTHESIZED THAT TRIPLE NEGATIVE BREAST CANCER RESULTED FROM THE FAILURE OR DEFICIENCY IN PROTEOGLYCAN HEPARAN SULFATE FROM CONGENITAL REASON OR AN IMMUNE DEFICIENCY,  THIS UNFORTUNATELY LEADS TO A RELATIVE RESISTANCE OF ESTROGEN RECEPTORS TO TUMOR GROWTH FACTOR BETA..==========================================
============================

Like any other resistance to conquer, the cell will increase the relative secretion of TGF beta with devastating consequences!  While failing to efficiently stimulate the Estrogen receptor, through SP1, TGF-BETA will stimulate the Aryl Hydrocarbon receptor which is normally "dormant" in the cytosol, stimulation of AHR not only renders the cell susceptible to

natural plant flavonoids, polyphenolics and indoles, as well as synthetic polycyclic aromatic hydrocarbons and dioxin-like compounds. AhR is a cytosolic transcription factor that is normally inactive,(see references)

but the increase of TGF induced Sp1 activity wakes this receptor up!

but also this receptor through ARNT, will induce the expression of genes such as Hsp90 (the stress gene--waking up the NF-kB), CYP (the modulator of estrogen and other ) but also all the genes interacting with Sp1,  including 

RELA,[66][67] cyclin T1,[68]SRC-1,[69] retinoblastoma protein,[70] NRIP1,[71] estrogen receptor alpha,[72][73] NEDD8[74] and ARNTL.[75]


The RELA gene

 

NFKB1 (MIM 164011) or NFKB2 is bound to REL , RELA (this gene), or RELB to form the NF-κB complex. The p50 (NFKB1)/p65 (RELA) heterodimer is the most abundant form of NF-κB. The NF-κB complex is inhibited by IκB (NFKBIA, or NFKBIB), which inactivates NF-κB by trapping it in the cytoplasm. Phosphorylation of serine residues on the I-kappa-B proteins by kinases (IKBKA or IKBKB) marks them for destruction via the ubiquitination pathway, thereby allowing activation of the NF-κB complex. Activated NF-κB complex translocates into the nucleus and binds DNA at kappa-B-binding motifs such as 5-prime GGGRNNYYCC 3-prime or 5-prime HGGARNYYCC 3-prime (where H is A, C, or T; R is an A or G purine; and Y is a C or T pyrimidine).[2]

Interactions

RELA has been shown to interact with:

 Just the rela gene will create a havoc! one important note several of these gene including the PRKC are upstream from DAB2 which is found depressed in Ovarian cancer!(see TGF-beta pathway as proposed by MSKCC)  The link is there!

Post a Comment