Showing posts with label carcinoma. Show all posts
Showing posts with label carcinoma. Show all posts

Tuesday, March 26, 2013

Hypothesis of small cell cancer pathogenesis

Hypothesis of small cell cancer pathogenesis
It seems that stimulation from smoking and stress acting through the FOS /c-JUNK will hit at nuclear level, genes of differentiation such FHIT,( The gene encompasses the common fragile site FRA3B on chromosome 3, where carcinogen-induced damage can lead to translocations and aberrant transcripts of this gene. In fact, aberrant transcripts from this gene have been found in about half of all esophageal, stomach, and colon carcinomas.

It also known as human accelerated region 10.)  (wikipedia)
FHIT will in turn affect UBE2I, the SUMO-conjugating enzyme altering this way ubiquitination
But UBE1I also affect a Myriad of important genes that will start and amplify the neoplastic process:
UBE2I has been shown to interact with WT1,[3] TOP1,[4] RAD51,[5][6] Activating transcription factor 2,[7] PIAS1,[8][9][10] SALL1,[11] FHIT,[12] RANBP2,[13][14] Protein inhibitor of activated STAT2,[8][15] DNMT3A,[16] DNMT3B,[17] Small ubiquitin-related modifier 1,[6][13][18][19] SAE2,[13][20] RANGAP1,[13][18][20] Death associated protein 6,[20][21] Androgen receptor,[22] ETS1,[23] IPO13,[24] TCF3,[25] TNFRSF1A,[26] DACH1,[15][27] P53,[6][19][28][29] BLMH,[30] MAP3K1[26] and Microphthalmia-associated transcription factor.[31] (wikipedia)

Top 1 and Rad1: these affects BRCA and other genes of DNA repair including P53.  The neoplastic process wants tolerance of gene abnormalities in neoplastic cells.  Methylation of FHIT is critical for cancer to mature!

also...