Steve Anderson Professor and Director Biomedical Sciences Program Molecular Biology Ph.D., The Rockefeller University, 1981 Campus Box 8104 Cancer Research Tower (RC1-South), Room 5121 Phone: 303-724-3742 steve.anderson@uchsc.edu

My lab is interested in signal transduction by tyrosine kinases, with a particular emphasis upon members of the Src family of tyrosine kinases. We primarily work on the receptor for prolactin. Prolactin stimulates the proliferation and differentiation of mammary epithelial cells, and perhaps is best known for stimulating the transcription of milk protein genes. Prolactin also maintains the viability of mammary epithelial cells during lactation by suppressing programmed cell death. We have demonstrated that Src-like kinases are required for activation of mitogenic and anti-apoptotic signaling pathways downstream of both of these receptors. Specifically, Src-like kinases appear to regulate the activation of phosphatidylinositol 3-kinase and the subsequent activation of the anti-apoptotic protein kinase Akt. We are currently determining the mechanism by which Src-like kinases are activated and what intermediates regulate Akt activation. This includes an analysis of mammary gland development in mice that lack expression of specific Src family kinases.

Our interest in Akt has also led us to examine the role of Akt in mammary gland development and tumorigenesis. We have generated transgenic mice that express a constitutively activated mutant of Akt in mammary gland and have demonstrated that Akt significantly delays mammary gland involution, an apoptotic process in which perhaps 80% of mammary epithelial cells die. In addition, it appears that a preneoplatic state is established in these mice which predisposes them to mammary cancer. We are currently characterizing these mice to identify potential substrates for Akt, as well as genes whose transcription maybe regulated by Akt. Future studies will address what oncogenes cooperate with Akt in generating mammary tumors, and whether Akt is activated in human breast cancer.

Selected Publications

Schwertfeger KL, Hunter S, Heasley LE, Leon RP, DeGregori J, and Anderson SM (2001) Prolactin stimulates activation of c- jun N-terminal kinase (JNK). Mol. Endocrinol., 15 :867-881.

Schwertfeger KL, Richert MM, and Anderson, SM (2001) Mammary gland involution is delayed by activated Akt in transgenic mice. Mol. Endocrinol. 15, 867-881.

Boonyaratanakornkit V, Scott MP, Ribon V, Sherman L, Anderson SM, Maller JL, Miller WT, and Edwards, DP (2001) Progesterone receptor contains a proline-rich motif that directly interacts with SH3 domains and activates c-Src family tyrosine kinases. Mol. Cell 8 :269-280.

Kassenbrock CK, Hunter S, Garl PM, Johnson GL, and Anderson SM, 2002. “Inhibition of Src family kinases blocks EGF-induced activation of Akt, phosphorylation of Cbl, and ubiquitination of the EGF receptor.” Journal of Biological Chemistry 277: 24967-24975.

Limesand, KH, Barzen KA, Quissell DO, and Anderson SM (2003) Synergistic suppression of apoptosis in salivary acinar cells by IGF1 and EGF: Role of Akt. Cell Death and Differentation, in press.

Sun W, Wei X, Kesavan K, Garrigton TP, Fan R, Mei J, Anderson SM, Gelfand EW, and Johnson GL (2003) MEKK2 and the adapter protein Lad regulate ERK5 activation by EGF via Src. Molecular and Cellular Biology, in press.

Latest Publications in PubMed