FURTHER EXPLORATION INTO THE GENES OF PROSTATE CANCER

Prostate cancer is one of the most interesting cancers from research perspective.  It has high Incidence but only 1 in seven patients diagnosed with it dies.  In 2011, close to 241,000 people were diagnosed with this cancer but only 34,000 died of this disease.  This fact points to the fact that some of the pathology in this disease,  has clearly an indolent course while other cases have a virulent course.  The Challenge remains how to best diagnosed those with the virulent course because they require multi-modality therapy for a cure.  It is believed that the virulence status of the disease can be attributed to a mean and bad genetic profile, but to this date the exact profile is being debated.  What is known or currently accepted is that "there is a loss of function of genes that detoxify carcinogens" leading to hypermethylation and silencing of some critical genes which include that of the "PI class Gluthation-S-transferase." (ASCO).

Then there is the fusion of TMPRSS2 with ERG or ETS.  Mutation at SPINK-1  and the involvement RAF kinase are not small businesses!   The RAF Kinase amplification ensures the survival of the disease because with the MAPK (and a little bit of the MTOR) downstream, this pathways is anti-apoptotic.  Therefore it ensures the survival of Prostatic cancer cells.   The SPINK1 is globally a control gene which represses Catalytic enzymes (such as Trypsin) in order to control their activity and keep their activities within normal range.  With SPINK-1 Mutated, there is an uncontrolled cleavage of gene target substrates by relevant Proteases!   and Guess what?  TMPRSS-2 is just such a PROTEASE.
(wikipedia on TMPRSS2-"The protease domain of this protein is thought to be cleaved and secreted into cell media after autocleavage. The biological function of this gene is unknown.^{[2]")
The association of TMPRSS2 with ERG amplify the action of TMPRSS2.  Yes ERG give the Multiplication power of Red cell to a protease.  A multiplied TMPRSS2 product, a protease, goes  to work on its targets and the rest is History!  It will amplified IL-2, CDK 10, splicing factors (SF3B4 which acts on TOP2A), CHEK1, BMPR1A,and CDC5L and DNA-PKC, CID and CHUK!  Through ZMYND1 it activates C11orf30 and blocks BRAC2 to remove gene repair function and cellular tolerance of genetic errors.  Basically the neoplastic process is set and through BMP, metastasis to the bone is set to occur!
With this understanding-please go to work!
The CRBCM is on your side!
HOW MUCH THE KU HELPS TEMPRSS2 IN ITS LOCALIZATION AT NUCLEAR LEVEL IS STILL TO BE DEFINED!  IF VERIFIED IT WILL MAKE THE KU A SUBSTANTIAL TARGET IN PROSTATE AND PANCREATIC CANCERS!}