Selected Publications

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Freeman, M.R., Bagli, D.J., Lamb, C.C., Guthrie, P.D., Uchida, T., Slavin, R.E., and Chung, L.W.K. (1994) Culture of a prostatic cell line in basement membrane gels results in an enhancement of malignant properties and constitutive alterations in gene expression. Journal of Cellular Physiology 158: 325-336.

Edelstein, R.A., Carr, M.C., Caesar, R.C., Young, M., Atala, A., and Freeman, M.R. (1994) Detection of human androgen receptor mRNA expression abnormalities by competitive PCR. DNA and Cell Biology 13: 165-273.

Blotnick, S., Peoples, G.E., Freeman, M.R., Eberlein, T.J., and Klagsbrun, M. (1994) T lymphocytes synthesize and export heparin-binding epidermal growth factor-like growth factor and basic fibroblast growth factor, mitogens for vascular cells and fibroblasts: Differential production and release by CD4+ and CD8+ T cells. Proc. Natl. Acad. Sci. USA 91: 2890-2894. 

Cilento, B.G., Freeman, M.R., Schneck, F.X., Retik, A.B., and Atala, A. (1994) Phenotypic and cytogenetic characterization of human bladder urothelia expanded in vitro. Journal of Urology 152:665-670.

Carr, M.C., Schlussel, R.N., Peters, C.A., Uchida, T., Mandell, J., and Freeman, M.R. (1995) Expression of cell growth regulated genes in the fetal kidney: Relevance to in utero obstruction. Journal of Urology 154:242-246.

Peoples, G.E., Blotnick, S., Takahashi, K., Freeman, M.R., Klagsbrun M., and Eberlein, T.J. (1995) T lymphocytes that infiltrate tumors and atherosclerotic plaques produce heparin-binding epidermal growth factor-like growth factor and basic fibroblast growth factor: a potential pathologic role. Proc. Natl. Acad. Sci. USA 92: 6547-6551.

Freeman, M.R. Schneck, F.X., Gagnon, M., Corless, C., Soker, S., Niknejad, K., Peoples, G.E., and Michael Klagsbrun. (1995) Peripheral blood T lymphocytes and T cells infiltrating human cancers express vascular endothelial growth factor: A potential role for T cells in angiogenesis. Cancer Research 55:4140-4145.

Freeman, M.R., Yoo, J.J., Raab, G., Soker, S., Schneck, F.X., Renshaw, A., Klagsbrun, M., and Atala, A. (1997) Heparin-binding EGF-like growth factor is an autocrine growth factor for human urothelial cells and is synthesized by epithelial and smooth muscle cells in the human bladder. Journal of Clinical Investigation 99:1028-1036.

Peters, C.A., Freeman, M.R., Fernandez, C.A., Shepard, J., Wiederschain, D.G., and Moses, M.A. (1997) Dysregulated proteolytic balance as the basis for excess extracellular matrix in fibrotic disease. American Journal of Physiology 272: (Regulatory Integrative Comp. Physiol.) R1960-R1965.

Freeman, M.R., Paul, S., Kaefer, M., Ishikawa, M., Adam, R.M., Renshaw, A.A., Elenius, K., and Klagsbrun, M. (1998) Heparin-binding EGF-like growth actor in the human prostate: Synthesis predominantly by interstitial and vascular smooth muscle cells and action as a carcinoma cell mitogen. Journal of Cellular Biochemistry 68:328-338. (Cover art).

Dethlefsen, S.M., Raab, G., Moses, M.A., Klagsbrun, M., and Freeman, M.R. (1998) Extracellular calcium influx stimulates metalloproteinase cleavage and secretion of heparin-binding EGF-like growth factor independently of protein kinase C. Journal of Cellular Biochemistry 69: 143-153.

Moses, M.A., Wiederschain, D., Loughlin, K.R., Zurakowski, D., Lamb, C.C., and Freeman, M.R. (1998) Increased incidence of matrix metalloproteinases in urine of cancer patients. Cancer Research 58:1395-1399.

Park, J.M., Borer, J.G., Freeman, M.R.§., and Peters, C.A. (1998) Stretch activates heparin-binding EGF-like growth factor expression in bladder smooth muscle cells. American Journal of Physiology 275: (Cell Physiol. 44): C1247-C1254. § (Corresponding author on this paper).

Park, J.M., Yang, T., Arend, L.J., Schnermann, J.B., Peters, C.A., Freeman, M.R., and Briggs, J. (1999) Obstruction stimulates COX-2 expression in bladder smooth muscle cells via increased mechanical stretch. American Journal of Physiology 276 (Renal Physiol. 45):F129-F136. (Cover art)

Park, J.M., Bauer, S.B., Freeman, M.R., and Peters, C.A (1999) Oxybutynin chloride inhibits proliferation and suppresses gene expression in bladder smooth muscle cells. Journal of Urology 162:1110-1114.

Duque, J.L.F., Loughlin, K.R., Adam, R.M., Kantoff, P.W., Zurakowski, D., and Freeman, M.R. (1999) Plasma levels of vascular endothelial growth factor are increased in patients with metastatic prostate cancer. Urology 54:523-527.

Nguyen, H.T., Park, J.M., Peters, C.A., Adam, R.A., Orsola, A., Atala, A., and Freeman, M.R. (1999) Cell-specific activation of the HB-EGF and ErbB1 genes by stretch in primary human bladder cells. In Vitro Cellular and Developmental Biology 35:371-375.

Lin, J., Adam, R.M., Santiestevan, E., and Freeman, M.R. (1999) The phosphatidylinositol 3’-kinase pathway is a dominant growth factor-activated cell survival pathway in LNCaP human prostate carcinoma cells. Cancer Research 59:2891-2897.

Park, J.M., Adam, R.M., Peters, C.A., Guthrie, P.D., Sun, Z., Klagsbrun, M., and Freeman, M.R. (1999) AP-1 mediates stretch-induced expression of heparin-binding EGF-like growth factor in bladder smooth muscle cells. American Journal of Physiology (Cell Physiol.) C294-301.

Haberoth, K.M, Kaefer, M., Retik, A.B., Freeman, M.R. and Bizios, R. (1999) The effects of sustained hydrostatic pressure on select bladder smooth muscle cell functions. Journal of Urology 162:2114-2118.

Borer, J.G., Park, J.M., Atala, A., Nguyen, H.T., Adam, R.M., Retik, A.B., Freeman, M.R. (1999) Heparin-binding EGF-like growth factor expression increases selectively in bladder smooth muscle in response to lower urinary tract obstruction. Laboratory Investigation 79:1335-1345.

Adam, R.M., Borer, J.G., Williams, B.J., Eastham, J.A., Loughlin, K.R., Freeman, M.R. (1999) Amphiregulin is coordinately expressed with heparin-binding epidermal growth factor-like growth factor in the interstitial smooth muscle of the human prostate. Endocrinology 140:5866-5875.

Kaefer, M., Vemulapalli, S., and Freeman, M.R. (2000) A nontoxic diphtheria toxin analogue inhibits neonatal bladder smooth muscle cell proliferation. Journal of Urology 163:580-584.

Nguyen, H.T., Bride, S.H., Badaway, A.B., Adam, R.M., Lin, J., Orsola, A., Guthrie, P.D., Freeman, M.R. .§ and Peters, C.A. (2000) Heparin-binding EGF-like growth factor is upregulated in the obstructed kidney in a cell- and region-specific manner and acts to inhibit apoptosis. American Journal of Pathology 156:889-898. § (Corresponding author on this paper).

Nguyen, H.T., Adam, R.M., Bride, S.H., Park, J.M., Peters, C.A., and Freeman, M.R. (2000) Cyclic stretch activates p38 SAPK2-, ErbB2- and AT1-dependent signaling in bladder smooth muscle cells. American Journal of Physiology (Cell Physiol.) 279:C1155-C1167.

Duque, J.L., Adam, R.M., Mullen, J.S., Lin, J., Richie, J.P., and Freeman, M.R. (2001) Heparin-binding EGF-like growth factor is an autocrine mediator of human prostate stromal cell growth in vitro. Journal of Urology 165:284-288.

Peng, J-G., Zhuang, L., Berger, U.V., Adam, R.M., Williams, B.J., Brown, E.M., Hediger, M.A., and Freeman, M.R. (2001) CaT1 expression correlates with tumor grade in prostate cancer. Biochemical and Biophysical Research Communications 282:729-734.

Lin, J., Hutchinson, L., Gaston, S.M., Raab, G., and Freeman, M.R. (2001) BAG-1 is a novel cytoplasmic binding partner of the membrane form of heparin-binding EGF-like growth factor: A unique role for proHB-EGF in cell survival regulation. Journal of Biological Chemistry 276:30127-30132.

Soker, S., Kaefer, M., Johnson, M., Klagsbrun, M., Atala, A., and Freeman, M.R. (2001) VEGF-mediated autocrine stimulation of prostate tumor cells coincides with progression to a malignant phenotype. American Journal of Pathology 159:651-659.

Adam, R.M., Orsola, A., and Freeman, M.R. (2001) A novel method for implantation of LNCaP prostate tumor cells under the renal capsule. In Vitro Cellular and Developmental Biology Animal 37:360-362.

Ayan, S., Roth, J.A., Freeman, M.R., Bride, S.M. and Peters, C.A. (2001) Partial ureteral obstruction dysregulates the renal renin-angiotensin system in the fetal sheep kidney. Urology (2001) 58:301-306.

Kim, J., Adam, R.M., and Freeman, M.R. (2002) Activation of the Erk mitogen-activated protein kinase pathway stimulates neuroendocrine differentiation in LNCaP cells independently of cell cycle withdrawal and STAT3 phosphorylation. Cancer Research 62:1549-1554. 

Orsola, A., Adam, R.M., Peters, C.A., and Freeman, M.R. (2002) The decision to undergo DNA or protein synthesis is determined by mechanical deformation in bladder smooth muscle cells. Urology 59:779-783. 

Zhuang, L., Lin, J., Lu, M.L., Solomon, K.R., and Freeman, M.R. (2002) Cholesterol-rich lipid rafts mediate Akt-regulated survival in prostate cancer cells. Cancer Research 62:2227-2231. 

Adam, R.M., Kim, J., Lin, J., Orsola, A., Rice, D.C., and Freeman, M.R. (2002) Heparin-binding EGF-like growth factor stimulates androgen-independent prostate tumor growth and antagonizes androgen receptor function. Endocrinology 143:4599-4608.

Zhuang, L., Peng, J-B., Tou, L., Takanaga, H., Adam, R.M., Hediger, M.A., and Freeman, M.R. (2002) Calcium-selective ion channel, CaT1, is apically localized in gastrointestinal tract epithelia and is aberrantly expressed in human malignancies. Laboratory Investigation 82:1755-1764.

Lin, J. and Freeman, M.R. (2003) Transactivation of ErbB1 and ErbB2 receptors by angiotensin II in normal human prostate stromal cells. Prostate 54:1-7.

Stehr, M., Adam, R.M., Khoury, J., Zhuang, L., Solomon, K.R., Peters, C.A., and Freeman, M.R. (2003) Platelet-derived growth factor-BB is a potent mitogen for rat ureteral and human bladder smooth muscle cells: dependence on lipid rafts for cell signaling. Journal of Urology 169:1165-1170.

Adam, R.M., Danciu, T., McClellan, D.L., Borer, J.G., Lin, J., Zurakowski, D., Weinstein, M.H., Rajjayabun, P., Mellon, J.K., and Freeman, M.R. (2003) A nuclear form of the heparin-binding EGF-like growth factor precursor is a feature of aggressive transitional cell carcinoma. Cancer Research 63:484-490.

Danciu, T.E., Adam, R.M., Naruse, K., Freeman, M.R., and Hauschka, P.V. (2003) Calcium regulates the PI3K-Akt pathway in stretched osteoblasts. FEBS Letters 536:193-197.

Adam, R.M., Roth, J.A., Cheng, H-L., Rice, D.C., Khoury, J., Bauer, S.B., Peters, C.A., and Freeman, M.R. (2003) Signaling through PI3K-Akt mediates stretch- and PDGF-BB-dependent DNA synthesis in bladder smooth muscle cells. Journal of Urology 169:2388-2393.

Kim, J., and Freeman, M.R. (2003) JNK/SAPK mediates doxorubicin-induced differentiation and apoptosis in MCF-7 breast cancer cells. Breast Cancer Research and Treatment 79:321-328. 

Kim, J., Adam, R.M., Solomon, K.R., and Freeman, M.R. (2004) Involvement of cholesterol-rich lipid rafts in interleukin-6-induced neuroendocrine differentiation of LNCaP prostate cancer cells. Endocrinology 145:613-619.  

Cinar, B., Yeung, F. Konaka, H., Mayo, M.W., Freeman, M.R., Zhau, H.E., and Chung, L.W.K. (2004) Identification of a negative regulatory cis-element in the enhancer core region of the prostate specific antigen (PSA) promoter: Implications for intersection of androgen receptor and NF-kB signaling in prostate cancer cells. Biochemical Journal 379:421-431.  

Freeman, M.R. and Solomon, K.R. (2004) Cholesterol and prostate cancer. J. Cell. Biochem. 91:54-69. 

Stehr, M., Estrada, C., Khoury, J., Danciu, T., Sullivan, M.P., Peters, C.A., Solomon, K.R., Freeman, M.R. and Adam, R.M. (2004) Caveolae are negative regulators of TGFß1 signaling in ureteral smooth muscle cells. Journal of Urology 172:2451-2455.

Freeman, M.R. (2004) HER2/HER3 heterodimers in prostate cancer: whither HER1/EGFR? Cancer Cell 6:427-428.  

Kim, J., Adam, R.M., Solomon, K.R., and Freeman, M.R. (2004) Involvement of cholesterol-rich lipid rafts in interleukin-6-induced neuroendocrine differentiation of LNCaP prostate cancer cells. Endocrinology 145:613-619.  

Stehr, M., Estrada, C., Khoury, J., Danciu, T., Sullivan, M.P., Peters, C.A., Solomon, K.R., Freeman, M.R. and Adam, R.M. (2004) Caveolae are negative regulators of TGF b 1 signaling in ureteral smooth muscle cells. Journal of Urology 172:2451-2455.  

Adam, R.M., Eaton, S.H., Estrada, C., Nimgaonkar, A., Shih-S-C, Smith, L.E.H., Kohane, I.S., Bagli, D, and Freeman, M.R. (2004) Mechanical stretch is a highly selective regulator of gene expression in human bladder smooth muscle cells. Physiological Genomics 20:36-44.  

Orsala, A., Estrada, C.R., Nguyen, H.T., Retik, A.B., Freeman, M.R., Peters, C.A. and Adam, R.M. (2005) Growth and stretch response of human exstrophy bladder smooth muscle cells: Molecular evidence of normal intrinsic function. BJU, International (British Journal of Urology). 95:144-148.  

Zhuang, L., Kim, J., Adam, R.M., Solomon, K.R., and Freeman, M.R. (2005) Cholesterol targeting alters lipid raft composition and cell survival in prostate cancer cells and xenografts. Journal of Clinical Investigation 115:959-968.  

Cinar, B., De Benedetti, A., and Freeman, M.R. (2005) Post-transcriptional regulation of the androgen receptor by the mammalian target of rapamycin. Cancer Research 65:2547-2553.  

Marcus, K., Johnson, M., Adam, R.M., O’Reilly, M.S., Donovan, M., Atala, A., Freeman, M.R., and Soker, S. (2005) Tumor cell-associated neuropilin-1 and VEGF expression as determinants of tumor growth in neuroblastoma. Neuropathology 25, 178-187.  

Kim, J., Lin, J., Adam, R.M., Lamb, C., Shively, S.B., and Freeman, M.R. (2005) An oxidative stress mechanism mediates chelerythrine-induced heparin-binding EGF-like growth factor ectodomain shedding. Journal of Cellular Biochemistry 94:39-49.  

Freeman, M.R., Cinar, B., and Lu, M.L. (2005) Membrane rafts as potential sites of nongenomic hormonal signaling in prostate cancer. Trends in Endocrinology and Metabolism 16:273-279. 

MacLellan, D.L., Steen, H., Adam, R.M., Garlick, M., Zurakowski, D., Gygi, S.P., Freeman, M.R. and Solomon, K.R. (2005) A quantitative proteomic analysis of growth factor-induced compositional changes in lipid rafts of human smooth muscle cells. Proteomics 5:4733-4742.

Kim, J., Adam, R.M., and Freeman, M.R. (2005) Trafficking of nuclear HB-EGF into an epidermal growth factor receptor-dependent autocrine loop in response to oxidative stress. Cancer Research 65:8242-8249.

Estrada, C., Salanga, M., Bielenberg, D.R., Harrell, W.B., Zurakowski, D., Zhu, X., Palmer, M., Freeman, M.R. and Adam, R.M. (2006) Behavioral profiling of human transitional cell carcinoma ex vivo. Cancer Research 66:3078-3086.

Dimitrakov, J.D., Kaplan, S., Kroenke, K., Jackson, J.L., and Freeman, M.R. (2006) Treatment of chronic prostatitis/chronic pelvic pain syndrome: An evidence-based approach. Urology 67:881-888.

Freeman, M.R., Solomon, K.R. ,and Moyad, M. (2006) Statins and the risk of cancer. JAMA 295:2720-2721 (letter).

Hager, M., Solomon, K.R., and Freeman, M.R. (2006) The role of cholesterol in prostate cancer. Current Opinion in Clinical Nutrition and Metabolic Care 9:379-385.

Farokhzad, O.C., Dimitrakov, J.D., Karp, J.M., Khademhosseini, A., Freeman, M.R., Langer, R. (2006) Drug delivery systems in urology—getting “smarter”. Urology 68:463-469.

Fang PK., Solomon KR., Zhuang L., Qi M., McKee M., Freeman MR., Yelick PC. Caveolin-1alpha and -1beta perform nonredundant roles in early vertebrate development. Am J Pathol. 2006 Dec;169(6):2209-22.

Mukhopadhyay, N., Ferdinand, A.S., Mukhopadhyay, L., Cinar, B. ,Lutchman, M., Richie, J.P., Freeman, M.R., and Liu B. C-S. (2006) Unraveling androgen receptor interactomes by an array-based method: Discovery of proto-oncoprotein c-Rel as a negative regulator of androgen receptor. Experimental Cell Research. 2006 Nov 15;312(19):3782-95.

Bianco, S.D.C., Peng, J-B., Takanaga, H., Suzuki, Y., Crescenzi, A. Kos,C.H., Zhuang, L., Freeman, M.R., Gouveia, C.H.A., Wu, J., Luo, H., Mauro, T., Brown, E.M., and Hediger, M.A. Marked disturbance of calcium homeostasis in mice with targeted disruption of the Trpv6 calcium channel gene. Journal of Bone and Mineral Research. 2007 Feb;22(2):274-85.

Estrada, C., Adam, R.M., Eaton, S., Bagli, D. and Freeman, M.R. (2006) Inhibition of EGFR signaling abrogates smooth muscle proliferation resulting from sustained distension of the urinary bladder. Laboratory Investigation 86:1293-1302.

Freeman, M.R., Cinar, B., Kim, J., Mukhopadhyay, N.K., Di Vizio, D., Adam, R.M., and Solomon, K.R. (2007) Transit of hormonal and EGF receptor-dependent signals through cholesterol-rich membranes. Steroids 72:210-217.

Bianco, S.D.C., Peng, J-B., Takanaga, H., Suzuki, Y., Crescenzi, A. Kos,C.H., Zhuang, L., Freeman, M.R., Gouveia, C.H.A., Wu, J., Luo, H., Mauro, T., Brown, E.M., and Hediger, M.A. (2007) Marked disturbance of calcium homeostasis in mice with targeted disruption of the Trpv6 calcium channel gene. Journal of Bone and Mineral Research 22:247-285.

Park, Y.S., Kim, J., Misonou, Y., Takamiya, R., Takahashi, M., Freeman, M.R. and Taniguchi, N. (2007) Acrolein induces cycooxygenase 2 and prostaglandin production in human umbilical vein endothelial cells: role of p38 MAP kinase and protein kinase Cd. Arteriosclerosis, Thrombosis and Vascular Biology 27:1319-1325.

Adam, R.M., Mukhopadhyay, N.K., Kim, J. Di Vizio, D., Cinar, B., Boucher, K., Solomon, K.R., and Freeman, M.R. (2007) Cholesterol sensitivity of endogenous and myristoylated Akt. Cancer Research 67:6238-6246. Selected as a Highlight of the issue.

Di Vizio, D., Sotgia, F., Williams, T.M., Hassan, G.S., Capozza, F., Frank, P.G., Pestell, R.G., Loda, M., Freeman, M.R., and Lisanti, M.P. (2007) Caveolin-1 is required for upregulation of fatty acid synthase (FASN), a tumor promoter, during prostate cancer progression. Cancer Biology and Therapy (In press, scheduled for August).

Mukhopadhyay, N.K., Cinar, B., Mukhopadhyay, L., Lutchman, M., Ferdinand, A.S., Chung, L.W.K., Adam, R.M., Ray, S.K., Leiter, A.B., Richie, J.P., Liu, B. C.-S., and Freeman, M.R. (2007) The zinc finger protein RREB-1 is a co-regulator of the androgen receptor: Implications for the role of the Ras pathway in enhancing androgenic signaling in prostate cancer. Molecular Endocrinology June 5 [Epub ahead of print].

Kim, J., Keay, S., Dimitrakov, J.D., and Freeman, M.R. (2007) p53 mediates interstitial cystitis antiproliferative factor (APF)-induced growth inhibition of human urothelial cells. FEBS Letters July 2.

Dimitrakov, JD, Kroenke, K., Steers, W.D., Berde, C., Zurakowski, D., Freeman, M.R., and Jackson, J.L. (2007) Pharmacologic management of painful bladder syndrome/interstitial cystitis: A systematic review. Archives of Internal Medicine (In press).

Cinar, B., Mukhopadhyay, N.K., Meng, G., and Freeman, M.R. (2007) Phosphoinositide 3-kinase-independent non-genomic signals transit from the androgen receptor to Akt1 in membrane raft microdomains. Journal of Biological Chemistry
[Epub ahead of print].

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