|Kathleen F. Arcaro
Associate Professor of Veterinary and Animal Sciences, University of Massachusetts
Ph.D.: Rutgers University
One of the goals of environmental toxicologists is to understand the relationship between exposure to toxicants and disease. The research in my laboratory focuses on a heterogeneous group of environmental pollutants referred to as “endocrine disruptors”. Endocrine disruptors may mimic, block, or alter the metabolism of endogenous hormones and have been implicated in the decline of amphibian populations and the etiology of some cancers. Many pesticides, herbicides, industrial pollutants, pharmaceuticals, and household products are potential endocrine disruptors.
The research in my laboratory is aimed at understanding the human health effects of exposure to complex mixtures of environmental pollutants with emphasis on estrogenic and antiestrogenic pollutants. There presently are three major funded projects in the lab: 1) breast milk as a marker of exposure, effect and breast cancer risk, 2) signaling pathways in estrogen receptor-negative breast cancer and, 3) bioassays for detection of endocrine disruptors in water ways.
Breast Milk and Breast Milk Cells: Biomarkers of Exposure, Effect and Genetic Susceptibility to Breast Cancer Breast milk is an ideal human fluid for studying the relationship between exposure to pollutants and breast cancer risk because it contains lipophilic compounds implicated in the etiology of breast cancer and exfoliated breast epithelial cells. We have ongoing studies in which we are analyzing the relationship between pollutants in milk and levels of DNA damage, changes in gene expression and promoter hypermethylation in the exfoliated breast epithelial cells.
Signaling Pathways in Estrogen Receptor-Negative Breast Cancer Estrogen receptor tumor status is an important clinical characteristic of breast cancer, which correlates with patients’ prognosis, response to hormone therapy, and overall survival. Tamoxifen, a landmark drug that acts as an anti-estrogen in the therapy of hormone-dependent breast cancers, reduces disease recurrence in patients with estrogen receptor-positive tumors, but is ineffective against estrogen receptor-negative tumors. Additionally, some tumors do not respond to tamoxifen treatment despite estrogen receptor-positive status, and some tumors that initially respond to tamoxifen eventually acquire tamoxifen-resistance resulting in a more aggressive tumor with poorer prognosis. Using a recently derived, tamoxifen-selected, estrogen receptor-negative breast cancer cell line, we have identified several genes that are differentially regulated in breast cancer. One gene, mitogen-inducible gene 2 (MIG2) is the subject of a recent publication.
Gene Expression in the Freshwater Japanese Medaka (Oryzias latipes): A Sensitive Biomarker for Exposure to Endocrine Disrupting Compounds The Japanese medaka is a small freshwater, temperate zone, fish that breeds readily in the laboratory and can tolerate local waters year round making it ideal for toxicological studies both in the laboratory and in the field. We are using medaka to develop and optimize sensitive, reliable, and inexpensive assays for detecting endocrine disrupting compounds in water ways. Many pollutants in water quickly concentrate in fish and can be measured by the changes in gene expression that they produce. Using real time reverse-transcriptase PCR we have found that exposing male medaka to concentrations as low as one picomolar of 17 b-estradiol for as little as 48 hours results in a significant increase in the estrogen-responsive gene, Vitellogenin. By examining the mRNA levels of Vitellogenin, and other estrogen-responsive genes in male medaka we can determine if they have been exposed to any estrogens in the water. Likewise, examination of mRNA levels of androgen- or dioxin-like-responsive genes can alert us to the presence of the pollutants in the water. Thus, medaka can serve as sentinels for the detection of endocrine disrupting compounds in water.
Williams KE, Anderton DL, Lee MP, Pentecost BT, Arcaro KF. 2014. High-density array analysis of DNA methylation in tamoxifen-resistant breast cancer cell lines.. Epigenetics. 9(2)
Faupel-Badger JM, Arcaro KF, Balkam JJ, Eliassen HA, Hassiotou F, Lebrilla CB, Michels KB, Palmer JR, Schedin P, Stuebe AM et al.. 2013. Postpartum Remodeling, Lactation, and Breast Cancer Risk: Summary of a National Cancer Institute-Sponsored Workshop.. J Natl Cancer Inst.
Fagan-Solis KD, Schneider SS, Pentecost BT, Bentley BA, Otis CN, Gierthy JF, Arcaro KF. 2013. The ras homolog gene family, member A (RhoA) pathway mediates MMP-2 and MMP-9-independent invasive behavior in a triple-negative breast cancer cell line.. J Cell Biochem.
Turk CM, Fagan-Solis KD, Williams KE, Gozgit JM, Smith-Schneider S, Marconi SA, Otis CN, Crisi GM, Anderton DL, Kilimann MW et al.. 2012. Paralemmin-1 is over-expressed in estrogen-receptor positive breast cancers.. Cancer cell international. 12(1):17.
Qin W, Zhang K, Kliethermes B, Ruhlen RL, Browne EP, Arcaro KF, Sauter ER. 2012. Differential expression of cancer associated proteins in breast milk based on age at first full term pregnancy.. BMC cancer. 12:100.
Sturgeon SR, Balasubramanian R, Schairer C, Muss HB, Ziegler RG, Arcaro KF. 2012. Detection of promoter methylation of tumor suppressor genes in serum DNA of breast cancer cases and benign breast disease controls.. Epigenetics : official journal of the DNA Methylation Society. 7(11):1258-67.
Arcaro KF, Browne EP, Qin W, Zhang K, Anderton DL, Sauter ER. 2012. Differential expression of cancer-related proteins in paired breast milk samples from women with breast cancer.. Journal of human lactation : official journal of International Lactation Consultant Association. 28(4):543-6.
Browne EP, Punska EC, Lenington S, Otis CN, Anderton DL, Arcaro KF. 2011. Increased promoter methylation in exfoliated breast epithelial cells in women with a previous breast biopsy.. Epigenetics : official journal of the DNA Methylation Society. 6(12):1425-35.
Moffatt LT, May CL, Studer KE, Reckhow DA, Arcaro KF. 2010. Effects of exposure water volume, depuration time, and feeding status on vitellogenin mRNA induction in male medaka (Oryzias latipes) exposed to 17 β-estradiol.. Ecotoxicology and environmental safety. 73(8):1835-41.
Wong CM, Anderton DL, Smith-Schneider S, Wing MA, Greven MC, Arcaro KF. 2010. Quantitative analysis of promoter methylation in exfoliated epithelial cells isolated from breast milk of healthy women.. Epigenetics : official journal of the DNA Methylation Society. 5(7):645-55.
Zhu Z-J, Carboni R, Quercio MJ, Yan B, Miranda OR, Anderton DL, Arcaro KF, Rotello VM, Vachet RW. 2010. Surface properties dictate uptake, distribution, excretion, and toxicity of nanoparticles in fish.. Small (Weinheim an der Bergstrasse, Germany). 6(20):2261-5.
Chompoosor A, Saha K, Ghosh PS, Macarthy DJ, Miranda OR, Zhu Z-J, Arcaro KF, Rotello VM. 2010. The role of surface functionality on acute cytotoxicity, ROS generation and DNA damage by cationic gold nanoparticles.. Small (Weinheim an der Bergstrasse, Germany). 6(20):2246-9.
Tao L, Kannan K, Wong CM, Arcaro KF, Butenhoff JL. 2008. Perfluorinated compounds in human milk from Massachusetts, U.S.A.. Environmental science & technology. 42(8):3096-101.
Gozgit JM, Pentecost BT, Marconi SA, Ricketts-Loriaux RSJ, Otis CN, Arcaro KF. 2007. PLD1 is overexpressed in an ER-negative MCF-7 cell line variant and a subset of phospho-Akt-negative breast carcinomas.. British journal of cancer. 97(6):809-17.
Johnson-Restrepo B, Addink R, Wong C, Arcaro K, Kannan K. 2007. Polybrominated diphenyl ethers and organochlorine pesticides in human breast milk from Massachusetts, USA.. Journal of environmental monitoring : JEM. 9(11):1205-12.
Reiner JL, Wong CM, Arcaro KF, Kannan K. 2007. Synthetic musk fragrances in human milk from the United States.. Environmental science & technology. 41(11):3815-20.
Gozgit J.M., Pentecost P.T., Marconi S.A., Otis C.N., Wu C., and Arcaro K.F. 2006, Use of an Aggressive MCF-7 Cell Line Variant, TMX2-28, to Study Cell Invasion in Breast Cancer: Altered Expression of MIG2 in Human Breast Carcinomas May Play a Role in Cancer Cell Invasion. Molecular Cancer Research, 4(12):905-913.
Gozgit J.M., Nestor K.M., Fasco M.J., Pentecost B.T. and Arcaro K.F. 2004, Polycyclic aromatic hydrocarbons induce estrogen receptor-mediated luciferase, but do not upregulate estrogen responsive genes in MCF-7 cells. Toxicology and Applied Pharmacology 196:58-67.
Ssempebwa J.C., Carpenter D.C., Yilmaz B., DeCaprio, A.P., O’Hehir, D.J. and Arcaro K.F. 2004, Waste crankcase oil: an environmental contaminant with potential to modulate estrogenic responses. J Toxicology and Environmental Health 67:1081-1094.
Carpenter, D.O., Arcaro, K.F., Spink, D.C. 2002, Understanding the human health effects of chemical mixtures. Environmental Health Perspectives, 110(S1): 25-42.
Arcaro, K.F., Gierthy, J.F. and Mackerer, C.R. 2001, Antiestrogenicity of clarified slurry oil and two crude oils in a human breast-cancer cell assay. Journal of Toxicology and Environmental Health, Part A 62:101-107.