Nachweis von Transforming growth factor (TGF)-beta 2 und TGF-beta 2 Rezeptor beim humanen Prostata-Karzinom

TGF≤2 ist ein Zytokin, das an den Serin-Threonin-Kinase-Rezeptor Typ II entweder niedrig-affin direkt oder hoch-affin mittels Präsentation durch den TGF≤-Rezeptor Typ III bindet. Durch diese Bindung aktiviert und rekrutiert der TGF≤-Rezeptor Typ II den TGF≤-Rezeptor Typ I und transphosphoryliert die...

Full description

Saved in:
Bibliographic Details
Main Author: Schmitt, Christina
Contributors: Konrad, Lutz (Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2008
Online Access:PDF Full Text
Tags: Add Tag
No Tags, Be the first to tag this record!

TGF≤2 is a Zytokin, which binds to the Serin Threonin Kinase receptor type II either low affin directly or high affin by means of presentation by the TGF≤ receptor type III. By this connection activate and recruit the TGF≤ receptor type II the TGF≤ receptor type I and transphosphoryliert these that leads again to the phosphorylation of the receptor-associated Smads. So activated thus TGF≤2 the Smad signal path and promotes the Expression of goal genes in the cell core. In the human prostate gland TGF≤2 restrains cell growth, the Proliferation of the epithelium and promotes or restrains the Apoptose. Since TGF≤2 possesses however normally mainly tumorsupprimierende effects, it is questionable, how it can come under effect of this ligand to a Karzinogenese. Since the TGF≤ receptor is essential type II for the signal transmission, the assumption lies close that here the signal is interrupted. For example a decreased Expression or a mutation of the receptor could lead not Responsivität “the Prostatakarzinomzellen to this „. In this study the TGF≤ receptor type II immune-histochemically at Prostatakarzinomschnitten were angefärbt and evaluated the intensity of the staining with consideration of different tumor parameters. In addition with the help of a ELISAs the serum concentration was measured by TGF≤2 with Prostatakarzinom patients. Also these results were evaluated with consideration of different tumor parameters. The ELISAs and stainings resulted in some trends and/or correlations. Thus the TGF≤2-Serumkonzentration and the protein Expression of the TGF≤ receptor type II rose when, organ-exceeding tumors and infiltration the urethralen Resektionskante spread further. With metastasierten tumors likewise the Expression of the receptor rose, with Fernmetastasen however sank the TGF≤2-Serumkonzentration. The wachstumsinhibierende signal of TGF≤2 is thus not blocked by a sinking Expression of the TGF≤ receptor type II. The missing TGF≤2-Effekt can have however also different causes. For example the signal transmission could be interrupted by means of the Smad signal path. Either proteins could react with Smad2 or Smad 3, so that these no more are not able to pass the signal on or a increased production of the inhibitorischen Smad7 could lead to a large inhibition of the signal transmission. TGF≤2 is by activation of other signal paths and evasion of the Smad signal path even able to work growth-promoting. The rise of the TGF≤2-Serumkonzentration with simultaneous increase of the propagation of the tumor could be thus a possible cause for the increase of the tumor propagation by increase of the Proliferation and lowering of the Apoptose. Since a further TGF≤2-Effekt is the reduction of the cell adhesion and increase of the cell mobility, it could promote thus the aggressiveness and Invasivität of the Prostatakarzinome. Questionable it is only why the TGF≤2-Serumkonzentration sinks with Fernmetastasen. The hypothesis was set up that the trends are tumor dependent for the rise of the concentration of TGF≤2 in the serum with more aggressive and organ-exceeding carcinomas and are the trend to the waste with Prostatakarzinomen with Fernmetastasen the general state of the patient to be perhaps attributed. The worse the general state of the patient became, the more sank everything its serum values. The question, whether one can use the TGF≤2-Serumkonzentration measured by means of ELISA as tumor markers beside the PSA, was answered in the negative. Since the concentrations differ only in very small values, the use of TGF≤2 would suggest many diagnostic errors as tumor markers too. In this study resulted no correlations, however some trends, which are perhaps verified with sensitiveren methods for the regulation by TGF≤2 in the serum, like for example a Immuno PCR, and a larger number of samples and thus TGF≤2 nevertheless still than tumor markers establish could.