Abnormal prostatic growth: Hormonal influence and characterization of nuclear structure during cancer development

• Main Author: Leman, Eddy Saputra
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01-01-2002
• Subjects: Molecular biology; Oncology; Pathology
• ISBN: 9780493999654; 0493999655

Androgens such as testosterone has been reported to play a crucial role in prostate development. In addition, vitamin D as a steroid hormone has been demonstrated to have anti-cancer properties by maintaining the differentiated phenotype of prostatic cells. The structure/architecture of the nucleus also plays an important role in maintaining the differentiated phenotype. The nuclear matrix contains nuclear matrix proteins that contribute to the preservation of nuclear shape and its organization. Since alterations in nuclear morphology are hallmarks of cancer, these alterations are believed to be associated with changes in the nuclear matrix protein composition. Taken together, it is hypothesized that hormonal regulation and changes in the nuclear structure may contribute to abnormal growth in the prostate, which may indeed result in development of prostate diseases including prostate cancer. In this dissertation, we examine the role of vitamin D as a steroid hormone in the growth and differentiation of the normal prostate. This study was approached by examining the effects of this steroid on the androgen receptor (AR) and vitamin D receptor (VDR) in the normal prostate epithelial cell line 267B-1 as well as in a rat model. To study changes in the nuclear structure associated with prostate cancer, differences in the nuclear matrix proteins (NMPs) associated with prostate cancer development in the TRAMP (transgenic adenocarcinoma of mouse prostate) model were also examined. Our findings indicate that both androgen and vitamin D receptors in the normal prostate can be regulated by 1,25 D as well as other androgens such as testosterone. This further supports the concept that 1,25 D is a steroid hormone, and along with other androgens may play a role in the growth and differentiation of normal prostate. With respect to changes in the nuclear structure, we identified a subset of nuclear matrix proteins that are associated with changes in the prostate from the normal state to neoplasia. Identification of these nuclear matrix proteins will potentially allow the development of novel markers that can characterize the various stages of prostate cancer development as well as determine ways in which the nuclear matrix changes can serve as potential therapeutic targets.