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Molecular and Cellular Biosciences at Wake Forest University

Wake Forest University Graduate School » Molecular and Cellular Biosciences

J. Mark Cline, D.V.M., Ph.D.

J. Mark Cline, D.V.M., Ph.D.
Education & Training BS North Carolina State University 1982 DVM North Carolina State University 1986 PhD North Carolina State University 1992 Residency Pathology - Anatomic New York State College Veternary Medicine 1988 Internship Pathology - Anatomic New York State College Veternary Medicine 1987 Memberships American Association of Cancer Research Radiation Research Society Society for Toxicologic Pathology Veterinary Cancer Society American Coll of Veterinary Pathologists American Veterinary Medical Association DVM Foundation for the Advancement of Veterinary and Comparative Pathology


Feneran AN, O'Donnell R, Press A, Yosipovitch G, Cline M, Dugan G, Papoiu AD, Nattkemper LA, Chan YH, Shively CA. Monkey see, monkey do: contagious itch in nonhuman primates. Acta Derm Venereol. 2013;93(1):27-29.



Hassan S, Karpova Y, Baiz D, Yancey D, Pullikuth A, Flores A, Register T, Cline JM, D'Agostino R Jr, Danial N, Datta SR, Kulik G. Behavioral stress accelerates prostate cancer development in mice. J Clin Invest. 2013;123(2):874-886.


Morimoto Y, Killeen J, Hernandez BY, Mark Cline J, Maskarinec G. Parity and expression of epithelial histopathologic markers in breast tissue. Eur J Cancer Prev. 2013;22(5):404-408.


Ethun KF, Wood CE, Cline JM, Register TC, Appt SE, Clarkson TB. Endometrial profile of bazedoxifene acetate alone and in combination with conjugated equine estrogens in a primate model. Menopause. 2013;20(7):777-784.


Wood CE, Boue SM, Collins-Burow BM, Rhodes LV, Register TC, Cline JM, Dewi FN, Burow ME. Glyceollin-elicited soy protein consumption induces distinct transcriptional effects as compared to standard soy protein. J Agric Food Chem. 2012;60(1):81-86.


Feneran AN, O'Donnell R, Press A, Yosipovitch G, Cline M, Dugan G, Papoiu A, Nattkemper L, Chan Y, Shively CA. Monkey see, monkey do: contagious itch in nonhuman primates [abstract]. J Invest Dermatol. 2012;132(Suppl 1):S39.



Wu M, Shi L, Cimic A, Romero L, Sui G, Lees CJ, Cline JM, Seals DF, Sirintrapun JS, McCoy TP, Liu W, Kim JW, Hawkins GA, Peehl DM, Xu J, Cramer SD.Suppression of Tak1 promotes prostate tumorigenesis. Cancer Res. 2012;72(11):2833-2843.


Cline JM, Brignolo L, Ford EW.Urogenital system


Clafshenkel WP, King TL, Kotlarczyk MP, Cline JM, Foster WG, Davis VL, Witt-Enderby PA. Morinda citrifolia (noni) juice augments mammary gland differentiation and reduces mammary tumor growth in mice expressing the unactivated c-erbB2 transgene. Evid Based Complement Alternat Med. 2012;2012():487423.


Stute P, Sielker S, Wood CE, Register TC, Lees CJ, Dewi FN, Williams JK, Wagner JD, Stefenelli U, Cline JM. Life stage differences in mammary gland gene expression profile in non-human primates. Breast Cancer Res Treat. 2012;133(2):617-634.


Schnatz PF, Nudy M, O'Sullivan DM, Jiang X, Cline JM, Kaplan JR, Clarkson TB, Appt SE. Coronary artery vitamin D receptor expression and plasma concentrations of 25-hydroxyvitamin D: their association with atherosclerosis. Menopause. 2012;19(9):967-973.


Dewi FN, Wood CE, Lampe JW, Hullar MAJ, Franke AA, Golden DL, Adams MR, Cline JM. Endogenous and exogenous equol are antiestrogenic in reproductive tissues of apolipoprotein E-null mice. J Nutr. 2012;142(10):1829-1835.


Johnson NA, Ho A, Cline JM, Hughes CL, Foster WG, Davis VL. Accelerated mammary tumor onset in a HER2/Neum mouse model exposed to DDT metabolites locally delivered to the mammary gland. Environ Health Perspect. 2012;120(8):1170-1176.



Schnatz PF, Nudy M, O'Sullivan DM, Jiang X, Cline JM, Kaplan JR, Clarkson TB, Appt SE. The quantification of vitamin D receptors in coronary arteries and their association with atherosclerosis. Maturitas. 2012;73(2):143-147.


Ethun KF, Wood CE, Register TC, Cline JM, Appt SE, Clarkson TB. Effects of bazedoxifene acetate with and without conjugated equine estrogens on the breast of postmenopausal monkeys. Menopause. 2012;19(11):1242-1252.


Robbins ME, Bourland JD, Cline JM, Wheeler KT, Deadwyler SA. A model for assessing cognitive impairment after fractionated whole-brain irradiation in nonhuman primates. Radiat Res. 2011;175(4):519-525.


Wood CE, Tannehill-Gregg SH, Chen Z, van Doorslaer K, Nelson DR, Cline JM, Burk RD. Novel betapapillomavirus associated with hand and foot papillomas in a cynomolgus macaque. Vet Pathol. 2011;48(3):731-736.


Willard SL, Daunais JB, Cline JM, Shively CA. Hippocampal volume in postmenopausal cynomolgus macaques with behavioral depression. Menopause. 2011;18(5):582-586.



Zhang H, von Schoultz B, Cline JM, Sahlin L. Distribution of cyclooxygenases 1 and 2 in the uterus and breast of cynomolgus monkeys--effects of hormone treatment. Menopause. 2011;18(9):1001-1009.


Hill GD, Moore AB, Kissling GE, Flagler ND, Ney E, Cline JM, Dixon D. Effects of hormonally active agents on steroid hormone receptor expression and cell proliferation in the myometrium of ovariectomized macaques. Toxicol Pathol. 2011;39(3):508-515.


Cheng CP, Cheng H-J, Zhou P, Masutani S, Callahan MF, Cline JM, Little WC. Is beta3-adrenoceptor (AR) a target for heart failure therapy? Evidence from beta3-AR knockout mice [abstract]. Circulation. 2011;124(21 Suppl):A12986.



Wood CE, Kaplan JR, Fontenot MB, Williams JK, Cline JM. Endometrial profile of tamoxifen and low-dose estradiol combination therapy. Clin Cancer Res. 2010;16(3):946-956.


Shahryarinejad A, Gardner TR, Cline JM, Levine WN, Bunting HA, Brodman MD, Ascher-Walsh CJ, Scotti RJ, Vardy MD. Effect of hormone replacement and selective estrogen receptor modulators (SERMs) on the biomechanics and biochemistry of pelvic support ligaments in the cynomolgus monkey (Macaca fascicularis). Am J Obstet Gynecol. 2010;202(5):485.e1-9.


Chen BJ, Deoliveira D, Spasojevic I, Sempowski GD, Jiang C, Owzar K, Wang X, Cline JM, Bourland JD, Dugan G, et al. Growth hormone mitigates against lethal irradiation and enhances hematologic and immune recovery in mice and nonhuman primates. PLoS ONE. 2010;5(6):e11056.


Yu W, Cline M, Maxwell LG, Berrigan D, Rodriguez G, Warri A, Hilakivi-Clarke L.Dietary vitamin D exposure prevents obesity-induced increase in endometrial cancer in Pten+/- mice. Cancer Prev Res (Phila Pa). 2010;3(10):1246-1258.


Steude JS, Maskarinec G, Erber E, Verheus M, Hernandez BY, Killeen J, Cline JM.Mammographic density and matrix metalloproteinases in breast tissue. Cancer Microenviron. 2010;3(1):57-65.


Chandra SA, Cline JM, Adler RR. Cyclic morphological changes in the beagle mammary gland. Toxicol Pathol. 2010;38(6):969-983.


Ethun KF, Wood CE, Appt SE, Cline JM, Chen H, Clarkson TB. Effects of combination therapy with bazedoxifene and conjugated equine estrogens on the endometrial and vaginal epithelium of surgically postmenopausal monkeys [abstract]. Endocr Rev. 2010;31(3 Suppl 1):S1303.


Hofling M, Ma L, Sahlin L, Haglund C, Nording S, von Schoultz B, Cline JM.Expression of the androgen receptor and syndecan-1 in breast tissue during different hormonal treatments in cynomolgus monkeys. Climacteric. 2009;12(1):72-79.


Wood CE, Register TC, Cline JM. Transcriptional profiles of progestogen effects in the postmenopausal breast. Breast Cancer Res Treat. 2009;114(2):233-242.


Wood CE, Cline M. Interactive effects of low-dose estradiol and tamoxifen on the postmenopausal primate endometrium and mammary gland [abstract]. Cancer Res. 2009;69(2 Suppl):219S.


Hilakivi-Clarke L, Yu W, Cline M, Rodriguez GC, Maxwell GL. Dietary vitamin D exposure reverses the effects of obesity-inducing high-fat diet on premalignant and malignant endometrial changes in Pten+/- mice [abstract]. Gynecol Oncol. 2009;112(2 Suppl 1):S14.


Muhammad FS, Goode AK, Kock ND, Arifin EA, Cline JM, Adams MR, Hoyer PB, Christian PJ, Isom S, Kaplan JR, Appt SE. Effects of 4-vinylcyclohexene diepoxide on peripubertal and adult Sprague-Dawley rats: ovarian, clinical, and pathologic outcomes. Comp Med. 2009;59(1):46-59.



Diez FR, Garrido AA, Sharma A, Luke CT, Stone JC, Dower NA, Cline JM, Lorenzo PS. RasGRP1 transgenic mice develop cutaneous squamous cell carcinomas in response to skin wounding: potential role of granulocyte colony-stimulating factor. Am J Pathol. 2009;175(1):392-399.


Wagner JD, Jorgensen MJ, Cline JM, Lees CJ, Franke AA, Zhang L, Ayers MR, Schultz C, Kaplan JR. Effects of soy vs. casein protein on body weight and glycemic control in female monkeys and their offspring. Am J Primatol. 2009;71(9):802-811.


Cline JM, Wood CE. Estrogen/isoflavone interactions in cynomolgus macaques (Macaca fascicularis). Am J Primatol. 2009;71(9):722-731.


Buse E, Cline JM, de Rijk EPCT, Van Esch E, Vidal JD, Weinbauer GF, Wood CE. A monograph on female reproductive pathophysiology in macaques [editorial]. Toxicol Pathol. 2009;36(7 Suppl):5S-6S.


Hardisty JF, Anderson DC, Brodie S, Cline JM, Hahn FF, Kolenda-Roberts H, Lele SM, Lowenstine LJ. Histopathology of the urinary bladders of cynomolgus monkeys treated with PPAR agonists. Toxicol Pathol. 2009;36(6):769-776.


Kolenda-Roberts H, Anderson D, Brodie S, Cline JM, Hahn F, Hardisty J, Lele S, Lowenstine L. Diagnostic criteria for peroxisome proliferator-activated receptor (PPAR) agonist-induced urothelial lesions in cynomolgus monkeys [abstract]. Toxicol Pathol. 2009;37(1):150.


Kolenda-Roberts H, Anderson D, Brodie S, Cline JM, Hahn F, Hardisty J, Lele S, Lowenstine L. Guidance for histopathologic detection of endocrine disruption of the female reproductive system in the updated OECD 28-day oral toxicity study in rodents (TG 407) [abstract]. Toxicol Pathol. 2009;37(1):150-151.


Mohanan S, Wagner JD, Kock ND, Kavanagh K, Cline JM. Hepatic Mallory-Denk body formation in a streptozotocin-treated vervet monkey (Chlorocebus aethiops) [abstract]. Toxicol Pathol. 2009;37(1):135-136.


Wood C, Hester J, Appt S, Cline M. Columnar cell lesions in the postmenopausal primate breast [abstract]. Toxicol Pathol. 2009;36(1):150-151.


Verheus M, Maskarinec G, Erber E, Steude JS, Killeen J, Hernandez BY, Cline JM.Mammographic density and epithelial histopathologic markers. BMC Cancer. 2009;9():art. 182.


Maskarinec G, Erber E, Verheus M, Hernandez BY, Killeen J, Cashin S, Cline JM.Soy consumption and histopathologic markers in breast tissue using tissue microarrays. Nutr Cancer. 2009;61(5):708-716.


Work in my laboratory focuses on histopathologic and immunohistochemical methods for characterization of pre-neoplastic lesions and neoplasms. My work concerns the effect of hormonal therapies (hormone replacement after menopause, oral contraceptives, and others) on breast and uterine cancer risk. This work involves the characterization of regulatory changes and pre-cancerous lesions in the endometrium and mammary gland of macaques receiving the various hormonal therapies. Endpoints in these studies are changes in expression of proliferation markers (for example, Ki-67), estrogen and progesterone receptors, growth factor receptors, markers of cell death (apoptosis), and the development of morphologically detectable preneoplastic changes. Soy isoflavones (phytoestrogens) are also being studied, as a dietary alternative to postmenopausal hormonal replacement therapy. Work to date indicates that hormonal regulation of the breast and endometrium differ in postmenopausal animals, and that the combined estrogen-progestin therapy that prevents endometrial cancer increases proliferation in breast epithelial cells and may therefore increase the risk of breast cancer. Our most recent and exciting results indicate that dietary soy supplementation may decrease estrogen-induced cell proliferation and cancer risk in the breast and uterus.



FIGURE 1: Breast epithelium stained with an antibody to the proliferation marker Ki67. Brown staining indicates proliferation and an associated increase in cancer risk. 


FIGURE 2: Ki67 (proliferation marker) staining of breast and endometrium, in animals given estrogen (E2) or a high-soy diet (Soy) or the combination. These results suggest that dietary soy may decrease breast and uterine cancer risk.