Breast cancer is the most frequent cancer in women and represents the second leading cause of cancer death among women. It is essential to better understand the mechanistic actions by which breast cancer occurs in order to develop new treatments. Therefore, my research is aimed at further elucidating the molecular pathways involved in the pathogenesis of breast cancer. For example, aberrant activation of the Wnt/beta-catenin signaling pathway contributes to the genesis of breast cancer.
I am interested in the secreted frizzled-related proteins (SFRPs) because they are a family of proteins that antagonize Wnt signaling and loss of SFRP expression is found in a multitude of cancers, including breast cancer. Our lab is investigating whether low SFRP levels might lead to breast cancer development in both humans and mice. I am currently utilizing a SFRP1 knockout mouse model to determine whether SFRP loss renders the mammary gland more susceptible to breast cancer development.
Additionally, we are manipulating the expression levels of SFRP in both immortal (non-malignant) mammary epithelial cell lines as well as breast cancer cell lines to determine the mechanisms by which SFRPs influence the various pathways that lead to tumorigenesis since both Wnt dependent and independent pathways are involved. For example, the SFRPs exhibit an apoptotic function in several different tissues and the anti-apoptotic effect of lost SFRP expression has been implicated in carcinogenesis. Therefore, my research also focuses on has SFRPs regulate the pathways that lead to cell death how they might be targeted for breast cancer treatment purposes.
Gregory KJ, Roberts AL, Conlon EM, Mayfield JA, Hagen MJ, Crisi GM, Bentley BA, Kane JJ, Makari-Judson G, Mason HS, Yu J, Zhu LJ, Simin K, Johnson JPS, Khan A, Schneider BR, Schneider SS, Jerry DJ. (2019) Gene expression signature of atypical breast hyperplasia and regulation by SFRP1. Breast Cancer Research. June 27; 21(1):7
Gregory KJ, Morin SM, Bentley B, Elsayad M, Crisi GM, Schneider SS (2018). The relationship between the calcium-sensing receptor and secreted frizzled related protein in the breast. J Molecular Oncology Research. 2 (2): 27-35
Gregory KJ, Morin SM, Schneider SS (2017) Regulation of Early Growth Response 2 expression by Secreted Frizzled Related Protein 1. BMC Cancer. July 7; 17(1):473
Roubert A, Gregory KJ, Li Y, Pfalzer AC, Li J, Schneider SS, Wood RJ, Liu Z (2017) The influence of tumor necrosis factor-α on the tumorigenic Wnt-signaling pathway in human mammary tissue from obese women. Oncotarget. May 30; 8 (22):36127-36136
Bassa LM, Jacobs C, Gregory KJ, Henchey E, Ser-Dolansky J, Schneider SS. (2016) Rhodiola crenulata induces an early estrogenic response and reduces proliferation and tumorsphere formation over time in MCF7 breast cancer cells. Phytomedicine Jan; 23(1): 87-94.
Gregory KJ and Sallie SS (2015). Estrogen-mediated signaling is differentially affected by the expression levels of SFRP1 in mammary epithelial cells. Cell Biology International July; 39(7): 873-879.
Gauger KJ, Bassa LM, Henchey EM, Wyman J, Ser-Dolansky, Shimono A, Schneider SS (2014). The effects of diet induced obesity on breast cancer associated pathways in mice deficient in Sfrp1. Molecular Cancer. May 22; 12(1):117.
Gauger KJ and Schneider SS. (2014). The tumor suppressor secreted frizzled related protein 1 regulates p53-mediated apoptosis. Cell Biology International. January; 38 (1): 124-130.
Dunphy KA, Seo JH, Kim DJ, Roberts AL, Tao L, DiRenzo J, Balboni AL, Crisi GM, Hagen MJ, Chandrasekaran T, Gauger KJ, Schneider SS, Jerry DJ (2013). Oncogenic transformation of mammary epithelial cells by Transforming Growth Factor beta independent of mammary stem cell regulation. Cancer Cell International. July 25; 13:74.
Gauger KJ, Bassa LM, Henchey EM, Wyman J, Bentley B, Brown M, Shimono A, Schneider SS (2013). Mice deficient in Sfrp1 exhibit increased adiposity, dysregulated glucose metabolism, and enhanced macrophage infiltration. Plos One December 5; 8:12.
Gauger KJ, Shimono A, Crisi CM, Schneider SS (2012). Loss of SFRP1 promotes ductal branching in the murine mammary gland. BMC Developmental Biology. August 28; 12:25.
Gauger KJ, Kerry L. Chenausky KL, Murray ME, Schneider SS (2011). Mammary epithelial cells with reduced levels of SFRP1 exhibit an increased sensitivity to TGF-β signaling by way of up-regulated ZEB2 expression. BMC Cancer. February 8; 11 (1): 59.
Gauger KJ, Rodríguez-Cortés A, Hartwich M, Schneider SS (2010). Rhodiola Crenulata inhibits the tumorigenic properties of invasive mammary epithelial cells with stem cell characteristics. Journal of Medicinal Plants Research. March 18; 4:6, 446-454.
Gauger KJ, Hugh JM, Troester MA, Schneider SS (2009). Down-regulation of SFRP1 in a mammary epithelial cell line promotes the development of a CD44high/CD24low population which is invasive and resistant to anoikis. Cancer Cell International. May 7; 9:11.
Gauger KJ, Giera S, Sharlin DS, Bansal B, Iannacone E, Zoeller RT (2007). Polychlorinated Biphenyls 105 And 118 Form Thyroid Hormone Receptor Agonists Following Cytochrome P4501A1 Activation In Rat Pituitary GH3 Cells. Environmental Health Perspectives 115 (Suppl 11), 1623-1611.
You SH, Gauger KJ, Bansal R, Zoeller RT (2006). 4-Hydroxy-PCB106 acts a direct thyroid hormone receptor agonist in rat GH3 cells. Molecular and Cellular Endocrinology 257-258: 26-34.
Gauger KJ, Kato Y, Haraguchi K, Lehmler HJ, Robertson LW, Bansal R, Zoeller RT (2004). Polychlorinated biphenyls (PCBs) exert thyroid hormone-like effects in the fetal rat brain but do not bind to thyroid hormone receptors. Environmental Health Perspectives 112 (Suppl) 5, 516-523.
Zoeller RT, Dowling ALS, Herzig CTA, Iannacone EA, Gauger KJ, Bansal R (2002). Thyroid hormone, brain development, and the environment. Environmental Health Perspectives 110 (Suppl 3):355-361.
Iannacone EA, Yan AW, Gauger KJ, Dowling AL, Zoeller RT (2002) Thyroid hormone exerts site specific effects on SRC-1 and N-CoR expression selectively in the neonatal rat brain. Molecular and Cellular Endocrinology 15: 186: 49-59.