UBC Theses and Dissertations
The progesterone receptors in human prostate Yu, Yue
The prostate composes of epithelium and stroma, both of which are kept in balance to maintain normal prostate function. The balance between epithelium and stroma can be disrupted by the abnormal growth of stromal cells which results in prostate diseases such as benign prostatic hyperplasia. The epithelial-stromal interaction plays important roles not only in normal prostate homeostasis maintaining but also in prostate cancer development and progression. In prostate tumor, cancer associated fibroblasts enhance the secretions of cytokines and growth factors to favor cancer cells growth and metastasis. Androgen receptors are reported to regulate the development and maintenance the function of prostate. Progesterone receptor (PR) which belongs to the same steroid hormone receptor family as androgen receptors are little known in prostate. PR was reported to express in prostate, but there is no clear conclusion about the localization and function of PR in human prostate. The objective of this thesis is to investigate the expression and function of PR in human prostate. Two PR isoforms, PRA and PRB, are detected in subsets of the human prostate stromal cells by applying immunohistochemistry assays. Both PR isoforms express specifically in human prostate stromal fibroblasts and smooth muscle cells. Both PRA and PRB are demonstrated to play an inhibitory role in prostate stromal cell proliferation. PR suppresses the expression of cyclin A, cyclinB and cdc25c to delay cell cycle. PRA and PRB are demonstrated to regulate different transcriptomes by gene microarray assay. Immunohistochemistry assays were applied to human prostate cancer tissue biopsies, and PR levels are detected to decrease in the cancer associated stroma compared to the paired normal stroma. The conditioned media from PR positive stromal cell inhibit PC-3 and C4-2B cell motility through down-regulating the secretion of stromal cell derived factor 1 and interleukin 6. We conclude that PRA and PRB express in prostate stromal cells and inhibit the stromal cells proliferation. Decreased expression of PR in cancer associated stroma contributes to prostate tumor progression.
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