published_or_final_version / Anatomy / Master / Master of Philosophy

(Uncorrected OCR) Abstract of thesis entitled Telomerase activation and telomeric repeats alteration in sex hormone-induced prostatic carcinogenesis in the Noble rat submitted by Chan Ching for the Degree of Master of Philosophy at the University of Hong Kong In November, 1998 Despite its distinction as the most frequently diagnosed cancer and the�second leading cause of cancer deaths in men, little is known about the causes and mechanisms of prostatic carcinogenesis. The animal model, based on the existing sex hormone-induced prostate carcinogenesis in the Noble rat, by substantially increasing the dosage of testosterone while keeping the level of estrogen unchanged has been reported. With this modified protocol, we have successfully induced high incidence of prostate carcinoma in Noble rats. The earliest time of development of dysplasia was two months, carcinoma in situ at 4 months and fully developed carcinoma at six months. The tumor incidence was 92% after 12 months hormonal implantation. This animal model is very useful in the investigation of prostate cancer as its multi -step nature mimics the human situation and its high incidence in relative short time. Telomerase activation is a characteristic of immortalized tumor cells and is thought to contribute to the mechanism by which these cells abort the normal process of senescence. Telomerase activity has been detected in various human cancers and there are reports showing that telomeric repeat fragment (TRF) length may be correlated to the staging of tumors. These findings suggested that telomerase activation and TRF length alteration might be useful in prognosis of different cancers. Study of prostate cancer on animal model can compensate for the difficulties in human cancer research, as stage-by-stage investigations are available. In this study, we proposed that telomerase would be activated in sex hormone-induced prostatic carcinogenesis and TRF length alterations might be correlated to the different stages of prostatic carcinogenesis. We have examined the telomerase activation as well as telomeric repeat fragment content alteration in the hormonal induced prostatic carcinogenesis in Noble rat. Telomerase activation is common in prostate carcinoma and also can be detected in 12% of non-malignant tissues. For the non-prostatic tissues tested, all the testis tissues (n=5) were strongly positive for telomerase activity and only one liver tissue (n=5) showed weak. telomerase activity. The high frequency of telomerase activation in prostatic carcinoma specimens suggested that it might be a useful malignancy marker for prognosis evaluation in prostatic carcinogenesis. There were alterations of TRF content in dorsal lateral prostate. The ventral prostate tissues have the similar results as the dorsal lateral prostate. It seems that the TRF content in normal tissues is less than that of hyperplasia, dysplasia and carcinoma tissues. However, no obvious relationships between the TRF content and clinicopathological properties of prostatic carcinogenesis were observed. Also, there was no significant relation between the telomerase activation and TRF content in this study. Hence, the TRF content appear to have no significant correlation with prostatic carcinogenesis. / abstract / toc / Anatomy / Master / Master of Philosophy

published_or_final_version / Anatomy / Master / Master of Philosophy

Yes / The membrane-type matrix metalloproteinases (MT-MMPs), an important subgroup of the wider MMP family, demonstrate widespread expression in multiple tumor types, and play key roles in cancer growth, migration, invasion and metastasis. Despite a large body of published research, relatively little information exists regarding evidence for MT-MMP expression and function in metastatic prostate cancer. This review provides an appraisal of the literature describing gene and protein expression in prostate cancer cells and clinical tissue, summarises the evidence for roles in prostate cancer progression, and examines the data relating to MT-MMP function in the development of bone metastases. Finally, the therapeutic potential of targeting MT-MMPs is considered. While MT-MMP inhibition presents a significant challenge, utilisation of MT-MMP expression and proteolytic capacity in prostate tumors is an attractive drug development opportunity.