Subspecialty	Endocrinology, Diabetes and Metabolism
Gender	Female
E-mail	alice.levine@mountsinai.org
Education and Training	MD, Columbia University College of Physicians & Surgeons
	Residency, Internal Medicine, Bellevue Hospital Center
	Residency, Internal Medicine, New York University
	Residency, Internal Medicine, Veterans Administration Med. Ctr.
	Fellowship, Endocrinology & Metabolism, Mount Sinai Hospital

Dr. Levine’s Research Laboratory focuses on understanding how hormones and growth factors coordinately regulate prostate growth in order to develop new treatment strategies for men with prostatic disorders.  Co-directed by Dr. Alexander Kirschenbaum, Clinical Associate Professor of Urology, her group were the first to publish on the successful management of benign prostatic hyperplasia with hormonal therapy.  They also reported that androgens increase stromal cell growth in the prostate and also regulate the powerful angiogenic factor, vascular endothelial cell growth factor (VEGF).  Dr. Levine’s group were also among the first to determine the cell-specific expression of cyclooxygenase-2 (COX-2) in the human prostate and to report that selective COX-2 inhibitors kill prostate cancer cells in vitro and in vivo.  They established the role of COX-2 in hypoxia mediated upregulation of survival and angiogenic proteins in human prostate cancer cells.  Dr. Levine’s group recently isolated and characterized a protein derived from dietary bitter melon seeds that selectively kills pre-neoplastic and neoplastic prostate cancer cells.  Her group has also published extensively on the mechanisms underlying prostate cancer bone metastases and are developing a bone-selective compound aimed at preventing and treating prostate cancer bone metastases.

Education and Training	MD, Columbia University College of Physicians & Surgeons
	Residency, Internal Medicine, Bellevue Hospital Center
	Residency, Internal Medicine, New York University
	Residency, Internal Medicine, Veterans Administration Med. Ctr.
	Fellowship, Endocrinology & Metabolism, Mount Sinai Hospital
Board Certification	Endocrinology, Diabetes and Metabolism

Subspecialty	Endocrinology, Diabetes and Metabolism
Board Certification	Endocrinology, Diabetes and Metabolism

Interactive roles of androgens and growth factors in human prostate development and neoplasia
This laboratory research program focuses on the interactive roles of androgens and growth factors in human prostate development and neoplasia. They have determined that keratinocyte growth factor (KGF) is produced by fetal prostate stroma and then targets fetal prostate epithelial cells resulting in differentiation. Stromal KGF production is upregulated by androgens. In addition, vascular endothelial growth factor (VEGF), a critical mediator of vasculogenesis in development and angiogenesis in cancer, is produced by fetal prostate stromal cells and is also upregulated by androgens. Their studies on prostate cancer demonstrate that stromal-epithelial interactions, under the influence of androgens, play a critical role in tumorigenesis. Human prostate cancer cells (LNCaP) will only grow subcutaneously in nude mice if co-inoculated with stroma or matrigel. However, they have demonstrated that these same cells will grow in nude mice without stromal co-inoculation if inoculated directly into bone. The bone stroma produces VEGF, which may support tumor growth by enhancement of angiogenesis. Stromal VEGF is regulated by androgens in vivo. Ongoing studies will determine 1) if androgens regulate VEGF in vivo and 2) the mechanism of action of androgens in regulating VEGF.

For more information, please visit the Levine Laboratory website.

Gabrilove JL, Levine AC, Kirschenbaum A, Droller MA. Effect of a GnRH analogue (leuprolide) on benigen prostatic hypertrophy. J Clin Endo Metab 1987; 6: 1331-1333.

Liu X, Yao S, Kirschenbaum A, Levine AC. NS398, a selective cyclooxygenase-2 inhibitor, induces apoptosis and down-regulates Bcl-2 expression in LNCaP cells. Cancer res 1998; 58: 4245-4249.

Liu X, Kirschenbaum A, Yao S, Lee R, Holland JF, Levine AC. Inhibition of cyclooxygenase-2 suppresses angiogenesis and growth of prostate cancer in vivo. J Urology 2000; 164: 820-825.

Liu X, Kirschenbaum A, Lu M, Yao S, Klausner A, Preston C, Holland J, Levine AC. Prostaglandin E2 stimulates prostatic intraepithelial neoplasis cell growth through activation of the interleukin-6/GP 130/STAT-3 signaling pathway.. Biochem & Biophys Research Comm 2002; 290: 249-255.

Liu X, Kirschenbaum A, Lu M, Yao S, Dosoretz A, Holland JF, Levine AC. Prostaglandin E2 induces hypoxia-inducible factor-1a stabilizationand nuclear localization in a human prostate cancer cell kine.. J. of Biol. Chem 2002; 277: 50081-50086.

Liu X, Kirschenbaum A, Yu K, Yao S, Levine AC. Cyclooxygenase-2 suppresses hypoxia-induced apoptosis via a combination of direct and indirect inhibition of p53 activity in a human prostate cancer cell line.. J Biol Chem 2005; 280: 3817-3823.

Liu X, Kirschenbaum A, Yao S, Levine AC. IL-6 and prostaglandin E2 signaling system results in enhancement of osteoclastogenesis through effects on the osteoprotegerin/receptor activator of nuclear factor-kb (RANK) ligand/RANK system. Endocrinology 2005; 146(4): 1991-1998.

Kirschenbaum A, Liu X, Yao S, Narla G, Friedman SL, Martignetti JA, Levine AC. Sex steroids have differential effects on growth and gene expression in primary human prostate epithelial cell cultures derived from the peripheral vs. transitionzones.. Carcinogenesis 2006; 27: 216-224.

Liu X, Kirschenbaum A, Yao S, Aaronson SA, Liu G, Levine AC, . Androgen-induced Wnt signaling activation in preosteoblasts promotes the growth of MDA-PCA-2b human prostate cancer cells.. Cancer research 2007; 67(12): 5747-5753.

Xiong SD, Yu K, Liu X, Yin LH, Kirschenbaum A, Yao S, Narla G, DiFeo A, Wu JB, Yuan Y, Ho S, Lam YW, Levine AC. Ribosome-inactivating proteins isolated from dietary bitter melon induce apoptosis and inhibit histone deacetylase-1 selectively in premalignant and malignant prostate cancer cells.. Int. J. Cancer 2009; 125: 774-782.