Accession Number : ADA494996


Title :   Mechanisms Down-Regulating Sprouty1, a Growth Inhibitor in Prostate Cancer


Descriptive Note : Final rept. 20 Sep 2004-19 Sep 2008


Corporate Author : HOWARD UNIV WASHINGTON DC


Personal Author(s) : Kwabi-Addo, Bernard


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a494996.pdf


Report Date : Oct 2008


Pagination or Media Count : 113


Abstract : The Sprouty gene family negatively regulates growth factor-induced receptor tyrosine kinase signaling in human prostate cancer (PCa). The purpose of this study was to investigate the expression of Sprouty1 in PCa, determine its biological function and elucidate the molecular mechanism(s) regulating its expression in PCa. RESULTS: Using immunohistochemical and quantitative RT-PCR analysis, I have shown that Sprouty1 is down-regulated in PCa tissues compared to matched normal prostate tissues. Transient forced expression of Sprouty1 significantly inhibited PCa proliferation, while stable over-expression of Sprouty1 was deleterious to PCa cell growth. I have shown by pyrosequencing and other methylation assays that DNA methylation of Sprouty1 promoter is a key mechanism for down-regulating Sprouty1 expression in PCa. Transcriptional studies have identified GATA and EGR transcription factors as key transcriptional repressors modulating Sprouty1 expression in PCa. CONCLUSION: I have demonstrated that the expression of Sprouty1, whose gene products encodes for a potential tumor suppressor activity is down-regulated in PCa. I have also shown DNA methylation and transcriptional repression to be key mechanisms for dys-regulating Sprouty1 expression in PCa.


Descriptors :   *PROSTATE CANCER , *DEOXYRIBONUCLEIC ACIDS , INHIBITORS , GENE EXPRESSION , GROWTH(PHYSIOLOGY) , METHYLATION , GENES , MOLECULES , CELLS(BIOLOGY)


Subject Categories : Biochemistry
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE