Assistant Professor
Department of Surgery
5841 S. Maryland Ave.
SBRI J557F/MC 5032
Chicago, IL 60637
Phone: 773-702-2990
Fax: 773-834-4546
Email:
Appointments
Committee
on Molecular Pathogenesis and Molecular Medicine,
Committee
on Cancer Biology
Committee on Cell Physiology
Education
B.A.: Chemistry, College of Wooster, Wooster, OH
Ph.D.: Cell Biology, Vanderbilt University, Nashville, TN
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Bibliography
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4T07 mouse mammary tumor cells express the APC tumor suppressor at the ends of long cell protrusions.
APC localizes to the luminal surface of alveolar epithelium in mammary tissues from day 16 wild-type lactating mice.
GFP-tagged APC localizes to the microtubule cytoskeleton in transfected Cos-1 cells.
Beta-catenin is stabilized in tumors from ApcMin/+ mice.
Inactivation of the APC tumor suppressor is a common and early event in human colorectal cancer and has been identified in breast cancer, among other tumor types. Mouse studies indicate that APC is required to maintain intestinal and mammary epithelial cell homeostasis, and its loss results in tumorigenesis in these tissues. Our overall objective is to identify the mechanism by which APC acts as a tumor suppressor in intestinal and mammary epithelial cells using both in vitro and in vivo approaches. Based on data from our laboratory and others, we are testing the working hypothesis that APC mediates epithelial cell polarity and survival in the mammary gland and intestine through mechanisms that do not involve beta-catenin-mediated gene regulation. Specific ongoing projects in the laboratory include:
1. manipulation of APC expression in non-transformed epithelial cells and cancer cells,
2. identification of APC-mediated effects in epithelial cells that are beta-catenin-dependent and -independent, and
3. characterization of defective mammary alveolar development in Apc-mutant mice.
In the long term, this work will contribute to the overall understanding of the APC/beta-catenin pathway in development and tumorigenesis and perhaps facilitate the design of novel therapeutic approaches to target this pathway in human cancers.
Mak GZ, Kavanaugh GM, Buschmann MM, Stickley SM, Koch M, Goss KH, Waechter H, Zuk A, Matlin KS. Regulated synthesis and functions of laminin 5 in polarized madin-darby canine kidney epithelial cells. Mol Biol Cell 2006; 17(8):3664-77 (PubMed)
Reichling T, Goss KH, Carson DJ, Holdcraft RW, Ley-Ebert C, Witte D, Aronow BJ, Groden J. Transcriptional profiles of intestinal tumors in Apc(Min) mice are unique from those of embryonic intestine and identify novel gene targets dysregulated in human colorectal tumors. Cancer Res 2005; 65(1):166-76 (PubMed)
Genter MB, Goss KH, Groden J. Strain-specific of alachlor on murine olfactory mucosal responses. Toxicol Pathol 2004; 32(6):719-25 (PubMed)
Liou GI, Samuel S, Matragoon S, Goss KH, Santoro I, Groden J, Hunt RC, Wang F, Miller SS, Caldwell RB, Rustgi AK, Singh H, Marcus DM. Alternative splicing of the APC gene in the neural retina and retinal pigment epithelium. Mol Vis 2004; 10:383-91 (PubMed)
Goss KH, Risinger MA, Kordich JJ, Sanz MM, Straughen JE, Slovek LE, Capobianco AJ, German J, Boivin GP, Groden J. Enhanced tumor formation in mice heterozygous for Blm mutation. Science 2002; 297(5589):2051-3 (PubMed)
Heppner Goss K, Trzepacz C, Tuohy TM, Groden J. Attenuated APC alleles produce functional protein from internal translation initiation. Proc Natl Acad Sci U S A 2002; 99(12):8161-6 (PubMed)
Heinen CD, Goss KH, Cornelius JR, Babcock GF, Knudsen ES, Kowalik T, Groden J. The APC tumor suppressor controls entry into S-phase through its ability to regulate the cyclin D/RB pathway. Gastroenterology 2002; 123(3):751-63 (PubMed)
Steinbrecher KA, Tuohy TM, Heppner Goss K, Scott MC, Witte DP, Groden J, Cohen MB. Expression of guanylin is downregulated in mouse and human intestinal adenomas. Biochem Biophys Res Commun 2000; 273(1):225-30 (PubMed)
Crawford HC, Fingleton BM, Rudolph-Owen LA, Goss KJ, Rubinfeld B, Polakis P, Matrisian LM. The metalloproteinase matrilysin is a target of beta-catenin transactivation in intestinal tumors. Oncogene 1999; 18(18):2883-91 (PubMed)
Shattuck-Brandt RL, Lamps LW, Heppner Goss KJ, DuBois RN, Matrisian LM. Differential expression of matrilysin and cyclooxygenase-2 in intestinal and colorectal neoplasms. Mol Carcinog 1999; 24(3):177-87 (PubMed)
Fingleton BM, Heppner Goss KJ, Crawford HC, Matrisian LM. Matrilysin in early stage intestinal tumorigenesis. APMIS 1999; 107(1):102-10 (PubMed)
Goss KJ, Brown PD, Matrisian LM. Differing effects of endogenous and synthetic inhibitors of metalloproteinases on intestinal tumorigenesis. Int J Cancer 1998; 78(5):629-35 (PubMed)
Zhang T, Nanney LB, Peeler MO, Williams CS, Lamps L, Heppner KJ, DuBois RN, Beauchamp RD. Decreased transforming growth factor beta type II receptor expression in intestinal adenomas from Min/+ mice is associated with increased cyclin D1 and cyclin-dependent kinase 4 expression. Cancer Res 1997; 57(9):1638-43 (PubMed)
Zhang T, Nanney LB, Luongo C, Lamps L, Heppner KJ, DuBois RN, Beauchamp RD. Concurrent overexpression of cyclin D1 and cyclin-dependent kinase 4 (Cdk4) in intestinal adenomas from multiple intestinal neoplasia (Min) mice and human familial adenomatous polyposis patients. Cancer Res 1997; 57(1):169-75 (PubMed)
Wilson CL, Heppner KJ, Labosky PA, Hogan BL, Matrisian LM. Intestinal tumorigenesis is suppressed in mice lacking the metalloproteinase matrilysin. Proc Natl Acad Sci U S A 1997; 94(4):1402-7 (PubMed)
Heppner KJ, Matrisian LM, Jensen RA, Rodgers WH. Expression of most matrix metalloproteinase family members in breast cancer represents a tumor-induced host response. Am J Pathol 1996; 149(1):273-82 (PubMed)
Wilson CL, Heppner KJ, Rudolph LA, Matrisian LM. The metalloproteinase matrilysin is preferentially expressed by epithelial cells in a tissue-restricted pattern in the mouse. Mol Biol Cell 1995; 6(7):851-69 (PubMed)
