Abstract
Background: Serine protease 23 (PRSS23) is a novel serine protease belong to the peptidase S1 family. Previous studies indicated that PRSS23 could be highly expressed in various cancers such as breast, thyroid and prostate tumors. However, the underlying mechanism of PRSS23 in tumor progression remains unclear. Our previous study indicated that PRSS23 is a downstream estrogen effector gene and mediates the proliferation of estrogen receptor positive breast cancer cells. We found that PRSS23 was also expressed in endometrioid adenocarcinoma by immunohistochemistry staining. This thesis study thus aims to investigate whether PRSS23 could be regulated by estrogen in endometrial cancer and affects its cell proliferation. Results: I found that PRSS23 was expressed in estrogen receptor positive human endometrial cancer cell line - Ishikawa. I further investigated the function of PRSS23 in Ishikawa cells by RNA inference systems. However, the RNA inference systems failed to generate PRSS23 knockdown Ishikawa cells. The gene expression of PRSS23 could be up-regulated under estrogen stimulation in MCF-7 cells, but not in Ishikawa cells. On the other hand, PRSS23 could be up-regulated in MCF-7 and Ishikawa cells under TPA (12-O-tetradecanoylphorbol-13-acetate)-induced AP-1(Activator protein-1) trans-activation. This is supported by the finding that the upstream promoter region of PRSS23 contains AP-1 protein binding site (TPA-response element; TRE) by bioinformatic prediction. Taken together, the possible transcriptional regulation of PRSS23 in MCF-7 cells might be regulated via ER□ dependent pathways. On the other hand, PRSS23 in Ishikawa cells might be regulated through estrogen but AP-1 dependent pathways. This study reveals the striking tissue specificity with distinct transcriptional regulation of PRSS23 by estrogen signaling in breast and endometrial cancer.