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:

• APBA2,^[3]
• AHR,^[4][5]
• ASCC3,^[6]
• BRCA1,^[7]
• BTRC,^[8]
• C-Fos,^[9]
• C-jun,^[9]
• C22orf25,^[10]
• CSNK2A1,^[11]
• CDK9,^[12]
• CEBPB,^[13][14]
• CREBBP,^{[15][16][17][18][19]}
• CSNK2A2,^[11]
• DHX9,^[20]
• EP300,^[19][21]
• ETHE1,^[22]
• FUS,^[23]
• HDAC1,^[16][21][24]
• HDAC2,^[21][25]
• HDAC3,^[26]
• ING4,^[27]
• IκBα,^{[8][21][26][28][29][30][31]}
• MEN1,^[32]
• MTPN,^[33]
• NCF1,^[34]
• NFKB1,^[35][36]
• NFKB2,^[35][37]
• NFKBIB,^[38][39]
• NFKBIE,^[40]
• NR3C1,^[41][42][43]
• NCOR2,^[44][45]
• PARP1,^[46]
• PIAS3,^[15]
• POU2F1,^[47]
• PPP1R13L,^[48][49]
• PRKCZ,^[50]
• REL,^[29][35][51]
• RFC1,^[52]
• RNF25,^[53]
• SP1,^[54][55]
• STAT3,^[56][57]
• TAF4B,^[58]
• TBP,^[59][60]
• TP53,^[57] and
• TRIB3.^{[61]" (wikipedia}
• 
  
• ^{note the NR3c1 (Androgen) where progestins intervene to amend estrogenic effects potentially!}

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)