Anderson Lab

Vice Chair for Research

James C. Todd Professor in Experimental Pathology

My lab is interested in signaling pathways that regulate mammary gland development and tumorigenesis. Our interest in mammary gland development has been stimulated by our studies of the MMTV-myr-Akt1 transgenic mice in which we observed that expression of activated Akt1 stimulated the precocious appearance of cytoplasmic lipid droplets during pregnancy. This stimulated us to examine the molecular switches in mice that regulate lipid biosynthesis at secretory activation, the transition from pregnancy to lactation. The major source of calories in mouse milk is present in the fat component, which is important for development of the nervous system as well as normal growth. The magnitude of the contribution of the fat present in mouse milk is revealed by the fact that an average mouse will secrete her entire body weight in milk fat. This fat is either derived from dietary fat, or is synthesized de novo from glucose. We are using genetically modified mice to examine the roles of various signaling molecules and transcription factors in regulating lipid biosynthesis in the lactating mammary gland. We have also learned that Akt is important in regulating involution of the mammary gland.

Crossing transgenic mice that express activated Akt (MMTV-myr-Akt1 transgenic mice) to MMTV-ErbB2 transgenic mice accelerates mammary tumorigenesis. MMTV-c-ErbB2 transgenic mice typically develop mammary tumors in 230 days; however bitransgenic mice expressing both c-ErbB2 and myr-Akt1 develop tumors in about 1110 days. We continue to characterize the molecular changes that underlie the accelerated tumorigenesis in these mice.Tumor cells are known to display an altered metabolism that is characterized by increased glucose uptake, an increase in glycolysis, and the increased secretion of lactate, a waste product of glycolysis. We have been examining the effect of altering the expression of the hexose transporter GLUT1 upon tumorigenesis in vivo. Inhibiting expression of GLUT1 decreases the initial growth of tumors in vivo, while overexpressing GLUT1 enhances tumor growth. We continue to probe the role of glucose in tumor metabolism and how modifying glucose flux may alter tumor growth. Since glucose is also critical in the lactating mammary gland, there may be important links between the metabolism of tumor cells and mammary epithelial cells during lactation.

Finally, in collaboration with Drs. MacLean, Schedin, and Thor, we are investigating the effects of obesity upon mammary tumorigenesis and whether restoring glucose balance and insulin sensitivity has an impact upon tumor growth in vivo. Since obesity is approaching epidemic proportions in our country, these studies have important clinical implications for the prevention and treatment of breast cancer.

Selected Publications (click publications to view)

1. K.L. Schwertfeger, M.M. Richert, and S.M. Anderson. 2001. “Mammary gland involution is delayed by activated Akt in transgenic mice.” Molecular Endocrinology, 15:867-881.

2. V. Boonyaratanakornkit, M. Porter-Scott, V. Ribbon, L. Sherman, S.M. Anderson, W.T. Miller, D.P. Edwards. 2001. “Progesterone receptor contains a specific proline-rich motif which directly interacts with SH3 domains and activates Src family tyrosine kinases.” Molecular Cell, 8:269-280.

3. K.L. Schwertfeger, J.P. McManaman, C. Palmer, M.C. Neville, and S.M. Anderson. 2003. “Expression of constitutively activated Akt in the mammary gland leads to excess lipid synthesis during pregnancy and lactation.” J. Lipid Research 44:1100-1112.

4. K.H. Limesand, K.L. Schwertfeger, and S.M. Anderson, 2006. “MDM2 is required for suppression of apoptosis by activated Akt1 in salivary acinar cells.” Molecular and Cellular Biology 26 : 8840-8856.

5. 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 -casein gene in mammary epithelial cells. Molecular Endocrinology 21:106-125.

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

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

Contact Information:

Phone: (303) 724-3742

Fax: (303) 724-3712

Email: Steve.Anderson@ucdenver.edu