Hope College Biology

Can Students at Hope College Help Find a Cure for Cancer?

We have cloned a novel, endothelium specific protein, VACM-1, which shares sequence homology with cullins, a family of intracellular proteins that regulate diverse cellular functions. Our work indicates that VACM-1 protein regulates cellular growth by a mechanism that distinguishes it from growth regulating factors, and from other cullins, and thus suggests a unique biological role for this largely uncharacterized cul gene product. In cancer cell line and in endothelial cells VACM-1 inhibits growth while expression of VACM-1 mutant has a dominant negative effect on cellular proliferation in vitro as it increases cellular growth, and, importantly, converts endothelial cells to the angiogenic phenotype. Consequently, VACM-1 may play a role as a potential novel suppressor of angiogenesis in vivo. Thus, the goal of our research is to test the hypothesis that VACM-1 is involved in the regulation of endothelial cell growth, and to identify the mechanism of VACM-1 regulated angiogenesis in vitro. Students will be involved in designing experiments that test different aspects of the functional relationships between VACM-1 and cellular growth under different extra-cellular environmental conditions. Students involved in our research projects will learn experimental procedures that include cell culture, immunocytochemistry, spectrophotometry, fluorescence polarization techniques, polyacrylamide gel analysis and Western blotting. Importantly, students will learn to read, discuss, and question research papers effectively and to prepare scientific manuscripts.

Representative Publications:

• Buchwalter* A, C. Van Dort*, R. Smith*, S. Schultz*, I. P. Le*, J. Abbott*, E, Oosterhouse, A. Johnson, F. Hansen-Smith, and M. Burnatowska-Hledin. 2007. Nedd-8 Modification of VACM-1/cul 5 induces MAPK phosphorylation and maspin degradation, and converts endothelial cells to the angiogenic phenotype. Microvascular Research. In Press.
• Johnson, A. E. *, I. P. Le*, A. Buchwalter* and M. A. Burnatowska-Hledin. 2007. Estrogen-dependent growth and estrogen receptor (ER)-alpha concentration in T47D breast cancer cells are inhibited by VACM-1, a cul 5 gene. Mol. Cell Biochem. 301:13-20.
• Sartor, A.*, J.B. Kossoris*, R. Wilcox*, R. Shearer*, A.E. Zeneberg*, P. Zhao, I. Lazdins and Maria A. Burnatowska-Hledin. 2006. Truncated form of VACM-1/cul 5 with an extended 3’ untranslated region stimulates cell growth via a MAPK-dependent pathway. BBRC 343:1086-1093.
• Burnatowska-Hledin, M.A., J.B. Kossoris*, C.J. Van Dort*, R. L. Shearer*, P. Zhao, D.A. Murrey*, J.L. Abbott*, C.E. Kan*, and C.C. Barney. 2004. T47 D Breast Cancer Cell Growth is Inhibited by Expression of VACM-1, a cul-5 Gene. Biochem. Biophys. Res. Commun. 319:817-825.
• Burnatowska-Hledin, M., J. Kossoris*, C. Van Dort*, D. Murrey* J. Abbott*, C. Kan*, and C. Barney. 2004. VACM-1 Expression in T47D Human Breast Cancer Cell Line. Biochem Biophys. Res. Com. 319: 817-825.
• Burnatowska-Hledin, M., A. Zeneberg*, A. Roulo*, J. Grobe*, P. Zhao, P.I. Lelkes, P. Clare, and C. Barney. 2001. Expression of VACM-1 protein in cultured rat endothelial cells is linked to the cell cycle. Endothelium. 8:49-63.
• Burnatowska-Hledin, M., P. Zhao, B. Capps*, A. Poel*, K. Parmelee*, C. Mungall*, A. Sharangpani*, and L. Listenberger*. 2000. VACM-1, a Cullin Gene Family Member, Regulates Cellular Signaling. Am. J. Physiol. Cell. Physiol. 279:C266-C273.

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