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Steven M. Anderson, Professor

Ph.D. (1981) The Rockefeller University

 
Department of Pathology
Molecular Biology

Campus Box 8104
Cancer Research Tower (RC1-South), Room 5121
Phone: 303-724-3742
steve.anderson@ucdenver.edu

 

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My lab is interested in signaling pathways that regulate mammary gland development and tumorigenesis. We are interested in events that regulate secretory activation at parturition and have focused our efforts on two different signaling molecules: the nonreceptor tyrosine kinase Src and the serine/threonine protein kinase Akt. We have learned that Src plays an important role in ductal elongation in the mammary gland during puberty that appears to be mediated by stromal cells in addition to mammary epithelial cells. Src null mice also exhibit delayed or incomplete lactogenesis which results in death of pups. The production of milk proteins in cultures of primary mammary epithelial cells isolated from Src null ice is severely reduced implying that Src has a role in regulating the transcription and/or translation of milk proteins genes.

We have previously generated transgenic mice that express activated Akt1 in the mammary gland because expression of Akt1 increases late in pregnancy and remains high throughout lactation. These transgenic mice exhibit precocious lipid biosynthesis and expression of milk protein genes during pregnancy, impaired lactation, and delayed involution doe to suppression of apoptotic pathways in the mammary gland. Analysis of the myr-Akt1 transgenic mice in comparison to normal mice has provided new insights into the regulation of secretory activation. This has provided new models that allow us to determine how the fat content of diet is sensed with regard to the synthesis of milk fat.

We also have found that expression of activated Akt in the mammary gland accelerates tumorigenesis by the Erbb2/Neu oncogene shorting tumor latency from 210 days to 100-110 days. Expression of Akt in these mammary tumors enhances aerobic glycolysis (the Warburg Effect). ErbB2 is overexpressed or mutated in about one-third of all human breast cancer patients, and mutants that lead to the activation of Akt occur in the majority of all breast tumors, thus providing an important clinical tie for this research. We are currently investigating the mechanisms that underlie the changes in tumor metabolism specifically with regard to glucose metabolism and fatty acid biosynthesis.

Our interest in tumor metabolism has lead to collaborative studies in which we wish to examine the effect of obesity upon mammary tumorigenesis, and whether restoring glucose balance with anti-diabetic drugs can inhibit tumorigenesis or the growth of existing tumors.

C.D. Young, A.S. Lewis, M.C. Rudolph, M.D. Ruehle, and S.M. Anderson, 2011. “Glut1 is required for efficient tumor growth by mouse mammary carcinoma cells.” PLOS One 6(8): e23205. Published on line August 3, 2011

M.C. Rudolph, T.D. Russell, M.C. Neville, and S.M. Anderson, 2011. “Prolactin-mediated regulation of lipid biosynthesis genes in vivo in the lactating mammary epithelial cell.” American Journal of Physiology-Endocrinology and Metabolism E1059-1068. PMID 21467304.

T. Yuan, Y. Wang, S.M. Anderson, and H. Gu, 2011 “Lactation defect in a widely used MMTV-Cre transgenic line of mice.” PLOS One 6(4): e19233. PMID 21559430

M.C. Rudolph, J. Monks, V. Burns, M. Phistry, R. Marians, M.R. Foote, D.E. Bauman, S.M. Anderson*, and M.C Neville*, 2010. “Sterol regulatory element binding protein (SREBPF-1) and dietary lipid regulation of fatty acid synthesis in the mammary epithelium.” American Journal of Physiology-Endocrinology and Metabolism 299(6): E918-927. PMID 20739508 (*denotes Co-senior authors)

B.L. Allen-Petersen, M.R. Miller, M.C. Neville, S.M. Anderson, K.I. Nakayama, and M.E. Reyland, 2010. “Role of protein kinase C delta in mammary gland development and apoptosis.” Cell Death and Disease. 1. e17 (21 January 2010) doi:10.1038/cddis.2009.20

Gacia-Martinez, J.M., A. Calcabrini, L. Gonzalez , E. Martin-Forero, M.T. Agullo-Ortuno, V. Simon, H. Watkin, S.M. Anderson, S. Roche, and J. Martin-Perez, 2010. ”A noncatalytic function of Src family kinases in prolactin-induced Jak2 signaling.” Cell Signaling 22: 415-426.

A.C. Nelson, T.R. Lyons, K.C. Hansen, L.A. Kiemele, C.D. Young, S.M. Anderson, and J.T. Holt, 2010. “AKT regulates BRCA1 stability in response to estrogen signaling.” Molecular and Cellular Endocrinology 319 (1-2): 129-142.

M.C. Rudolph, E.A. Wellberg, and S.M. Anderson, 2009. “Adipose depleted mammary epithelial organoid cells.” J. Mammary Gland Biology and Neoplasia 14: 381-386.

C.D. Young and S.M. Anderson, 2009. “Rah, rah, ROS: metabolic changes caused by loss of adhesion induce cell death.” Breast Cancer Research 11:307.

K.H. Limesand, S. Said, and S.M. Anderson, 2009. “Suppression of radiation-induced salivary gland dysfunction by IGF-1.” PLOS-One 4(3): e4663.

J.L. Malone, A.C. Nelson, R.C. Lieberman, K.A. Gibson, S.M. Anderson, and J.T. Holt, 2009. “Estrogen mediated phosphorylation and stabilization of BRCA2 protein in breast cancer.” Journal of Pathology 217: 380-388. Published online October 6, 2008 DOI:10.1002/path.2458

C.D. Young, E. Nolte, A. Lewis, N. Serkova, and S.M. Anderson, 2008. “Activated Akt1 accelerates mammary tumorigenesis in the MMTV-c-ErbB2 transgenic mice without activation of ErbB3.” Breast Cancer Research, 10 (4): R70. Highly Accessed Publication.

C.D. Young and S.M. Anderson, 2008. “Sugar and fat-that’s where it is at: metabolic changes in tumors.” Breast Cancer Research, 10(1): 202. Highly Accessed Publication.

H. Watkin, A. Lewis, M. Richert, M.C. Rudolph, J.L. McManaman, M.C. Neville, and S.M. Anderson, 2008. “Src-/- mice exhibit a profound lactation failure,” BMC Developmental Biology 8: 6. Highly Accessed Publication.

Buser, A.C., E. Handel-Gass, S.L. Wyszomeierski, W. Doppler, S.A. Leonhardt, J. Schaak, J.M. Rosen, H. Watkin, S.M. Anderson, and D.P. Edwards, 2007. Progesterone receptor repression of prolactin/Stat5-mediated transcription of the b-casein gene in mammary epithelial cells. Molecular Endocrinology 21:106-125.

M.C. Rudolph, J.L. McManaman, T. Phang, T. Russell, D.J. Kominsky, N.J. Serkove, S.M. Anderson, and M.C. Neville, 2007. “Metabolic regulation in the lactating mouse: A milk lipid synthesizing machine.” Physiological Genomics, 28: 323-336.

S.M. Anderson, M. Rudolph, J.L. McManaman, and M.C. Neville, 2007. ”Secretory activation: It’s not just about milk proteins synthesis!” 2007. Breast Cancer Research 9 (1): 204. Highly Accessed Publication.

T.R. Lyons, J. Thorburn, P.W. Ryan, A. Thorburn, S.M. Anderson, and C.K. Kassenbrock. “Regulation of the pro-apoptotic scaffolding protein POSH by Akt.” Journal of Biological Chemistry, 282: 21987-21997. Epub May 30, 2007.

M.C. Rudolph, M.C. Neville, and S.M. Anderson, 2007. ”Lipid synthesis in lactation: Diet and the fatty acid switch.” Journal of Mammary Gland Biology and Neoplasia, 12(4): 269-281.

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