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J. Julie Kim, PhDAssistant Professor
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Progesterone is essential for the regulation of normal female reproductive function. Its mode of action is diverse and dependent on the target tissues. In my lab we are interested in delineating the molecular mechanisms of progesterone action through its receptor, PR in the uterus. This is done in the context of normal endometrial differentiation, specifically, decidualization, as well as in uterine pathologies, such as endometriosis, endometrial cancer and uterine fibroids. Interestingly, in these three diseases, progesterone responsiveness is aberrant.
Specifically, we are interested in studying PR function in relation to other signaling pathways and transcription factors. We have demonstrated that the forkhead transcription factor FOXO1 is an important regulator of decidualization and that it synergistically regulates genes with PR. In endometrial cancer, the expression of FOXO1 is significantly downregulated and we hypothesize that this decrease contributes to the suboptimal response of the endometrium to progesterone. In uterine fibroids, progesterone promotes growth and we are studying potential mechanisms by which progesterone does this. Specifically the activation of the AKT pathway by progesterone is under investigation. Thus, we are studying diverse modes of action of PR both at the genomic and non-genomic levels in different uterine diseases. We hope to use the information generated from these studies towards the development of better therapies for endometriosis, endometrial cancer and uterine fibroids.
Takano M, Lu Z, Goto T, Fusi L, Higham J, Francis J, Withey A, Hardt J, Cloke B, Stavropoulou AV, Ishihara O, Lam EW, Unterman TG, Brosens JJ, Kim JJ. Transcriptional cross talk between the forkhead transcription factor forkhead box O1A and the progesterone receptor coordinates cell cycle regulation and differentiation in human endometrial stromal cells. Mol Endocrinol 2007; 21: 2334-2349.
Yin P, Lin Z, Cheng YH, Marsh EE, Utsunomiya H, Ishikawa H, Xue Q, Reierstad S, Innes J, Thung S, Kim JJ, Xu E, Bulun SE. Progesterone receptor regulates Bcl-2 gene expression through direct binding to its promoter region in uterine leiomyoma cells. J Clin Endocrinol Metab 2007; 92: 4459-4466.
Hoekstra AV, Kim JJ, Keh P, Schink JC. Absence of progesterone receptors in a failed case of fertility-sparing treatment in early endometrial cancer: a case report. J Reprod Med 2008; 53: 869-873.
Hoekstra AV, Ward EC, Hardt JL, Lurain JR, Singh DK, Buttin BM, Schink JC, Kim JJ. Chemosensitization of endometrial cancer cells through AKT inhibition involves FOXO1. Gynecol Oncol 2008; 108: 609-618.
Lu Z, Hardt J, Kim JJ. Global analysis of genes regulated by HOXA10 in decidualization reveals a role in cell proliferation. Mol Hum Reprod 2008; 14: 357-366.
Utsunomiya H, Cheng YH, Lin Z, Reierstad S, Yin P, Attar E, Xue Q, Imir G, Thung S, Trukhacheva E, Suzuki T, Sasano H, Kim JJ, Yaegashi N, Bulun SE. Upstream stimulatory factor-2 regulates steroidogenic factor-1 expression in endometriosis. Mol Endocrinol 2008; 22: 904-914.
Wang C, Norton JT, Ghosh S, Kim J, Fushimi K, Wu JY, Stack MS, Huang S. Polypyrimidine tract-binding protein (PTB) differentially affects malignancy in a cell line-dependent manner. J Biol Chem 2008; 283: 20277-20287.
Ward EC, Hoekstra AV, Blok LJ, Hanifi-Moghaddam P, Lurain JR, Singh DK, Buttin BM, Schink JC, Kim JJ. The regulation and function of the forkhead transcription factor, Forkhead box O1, is dependent on the progesterone receptor in endometrial carcinoma. Endocrinology 2008; 149: 1942-1950.
Berry E, Hardt JL, Clardy J, Lurain JR, Kim JJ. Induction of apoptosis in endometrial cancer cells by psammaplysene A involves FOXO1. Gynecol Oncol 2009; 112: 331-336.
Hoekstra AV, Sefton EC, Berry E, Lu Z, Hardt J, Marsh E, Yin P, Clardy J, Chakravarti D, Bulun S, Kim JJ. Progestins activate the AKT pathway in leiomyoma cells and promote survival. J Clin Endocrinol Metab 2009; 94(5):1768-74.
Morgan J,Hoekstra AV, Chapman-Davis E, Hardt JL, Kim JJ, Buttin BM. Synuclein-gamma (SNCG) may be a novel prognostic biomarker in uterine papillary serous carcinoma. 2009; 114(2):293-8.
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View Publications by Julie Kim listed in the National Library of Medicine (PubMed). |
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