Regulation of Pygopus (hPygo2) expression in prostate cancer by E74-Like factor 1 (Elf-1) transcription factor

Prostate cancer is a worldwide health concern. Pygopus2 (hPygo2) protein is required for growth in breast, ovarian, cervical and prostate cancer. hPygo2 expression is regulated by the Rb protein via the ETS factor Elf-1 in cervical and breast cancer. Additionally, the ETS family has confirmed roles in carcinogenesis and proliferation. The mechanism of hPygo2 expression has not been elucidated in prostate cancer. My hypothesis proposes that hPygo2 expression is regulated by Elf-1 bound to its promoter region. Prostate cancer cell lines were used to show protein levels of hPygo2, Elf-1 and ETS. ChIP assays confirmed varying binding capability of Elf-1 and ETS factors to the proximal promoter region between cell lines. Elf-1 knockdown experiments were performed, results show no change in hPygo2 protein levels but show reduction in 22Rv1 mRNA levels. These results suggest that Elf-1 might not be exclusively involved in the activation of Pygopus expression in prostate cancer.

The expression of Hsf1 in the rat myometrium during pregnancy and labour

Heat shock factor 1 (Hsf1) is a protein known to be involved in both stress and developmental processes through the regulation of heat shock proteins. However, to date, no studies have been performed on examining its expression in the myometrium during pregnancy. During pregnancy, the uterus undergoes many structural and functional changes, and it also endures both mechanical and hormonal stresses. Therefore, the purpose of this thesis was to characterize the expression of Hsf1, and its associated factors in the uterus during pregnancy. Immunoblot analysis determined that Hsf1 protein expression was high early in gestation (day (d) 6) and then decreased significantly from mid gestation onwards (specifically when compared to d15, d17 and d22, p<0.05, n=5). Immunofluorescence analysis, demonstrated that Hsf1 was readily detectable in the myometrium but did not markedly change over gestation. Hsf1 was also localized mainly in the cytoplasm of myometrial cells, with some granular staining in the nucleus. Many related proteins of Hsf1 were also detectable in the myometrium, during pregnancy, such as PARP-1 and Hsf2. These results indicate that Hsf1 could play an important role early in gestation either to aid in myometrial cell proliferation or to upregulate expression of key genes necessary for subsequent myometrial differentiation.