Carol A. Lange, Ph.D.

Research Interests:

Signal Transduction in Breast Cancer

Dr. Lange's laboratory is focused on the study of cross-talk between peptide growth factors and steroid hormone receptors in human breast cancer cells. The ovarian steroid hormones, estrogen and progesterone, as well as growth factor receptor tyrosine kinase-initiated signaling pathways are required for normal breast development, and these pathways also interact to influence breast tumorigenesis and breast cancer progression. Ongoing research projects in the laboratory include the study of the role of protein tyrosine kinases and mitogen acitivated protein kinase (MAPK) cascades in human breast cancer cell proliferation and survival, and their contribution to mechanisms of steroid hormone resistance in human breast cancer. In order to study problems in breast cancer cell biology, techniques in signal transduction, endocrinology, protein biochemistry and molecular biology are employed. Understanding the role of signaling cross-talk in cell growth control will provide useful information for the development of better strategies for the treatment of breast and other hormonally influenced and/or epithelial cell-derived cancers.

Selected Recent Publications:

• Daniel AR and Lange CL. 2009. Protein Kinases Mediate Ligand-Independent Derepression of Sumoylated Progesterone Receptors in Breast Cancer Cells. Proc. Natl. Acad. Sci. USA 106(34):14287-14292.

• Dressing GE and Lange CA. 2009. Integrated Actions of Progesterone Receptors and Cell Cycle Machinery Regulate Breast Cancer Cell Proliferation. Steroids 74(7): 573-576, (invited peer reviewed review).

• Hagan CR, Faivre EJ, and Lange CA. 2009. Scaffolding Actions of Membrane-Associated Progesterone Receptors. Steroids 74(7): 568-572, (invited peer reviewed review.

• Simon JA and Lange CA. 2008. Roles of the EZH2 Histone Methyltransferase in Cancer Epigenetics. Mutation Research. 647 (1-2): 21-29, (invited peer reviewed review)

• Lange CA. 2008. Challenges to Defining a Role for Progesterone in Breast Cancer. Steroids. 73 (9-10): 914-921.

• Lange CA. 2008. Integration of Progesterone Receptor Action with Rapid Signaling Events in Breast Cancer Models. J. Steroid Biochem. Mol. Biol. 108:203-212.

• Faivre EJ, Daniel AR, Hillard CJ, Lange CA. 2008. Progesterone Receptor Rapid Signaling Mediates Ser345 Phosphorylation and Tethering to Sp1 Transcription Factors. Mol Endo. 22(4): 823-837.

• Lange CA. 2007. Editorial:Membrane and Nuclear Steroid Hormone Receptors: two integrated arms of the same signaling pathway? Steroids. 72(2): 105-106.

• Daniel AR, Faivre EJ, and Lange CA. 2007. Phosphorylation-Dependent Antagonism of Sumoylation De-represses Progesterone Receptor Action in Breast Cancer Cells. Mol Endo, 21 (12); 2890-2906.

• Hanson Ostrander J, Daniel AR, Lofgren K, Kleer CG, and Lange CA. 2007. Breast Tumor Kinase (Brk/PTK6) Regulates Heregulin-Induced Activation of ERK5 and p38 MAP Kinases in Breast Cancer Cells. Cancer Research, 67(9); 4199-4209.

• Faivre E and Lange CA. 2007. Progesterone Receptors Upregulate Wnt-1 to Induce EGFR Transactivation and c-Src-depedenent Sustained Activation of ERK1/2 Mitogen-Activated Protein Kinase in Breast Cancer Cells. Mol. Cell. Biol. 27(2); 466-480.

• Daniel AR, Qiu M, Faivre EJ, Ostrander JH, Skildum A, Lange CA. 2007. Linkage of progestin and epidermal growth factor signaling: phosphorylation of progesterone receptors mediates transcriptional hypersensitivity and increased ligand-independent breast cancer cell growth. Steroids. Feb;72(2):188-201.

• Lange CA, Gioeli D, Hammes SR, Marker PC. 2007. Integration of Rapid Signaling Events with Steroid Hormone Receptor Action in Breast and Prostate Cancer.
   Annu Rev Physiol. 69:171-99.

• Faivre E, Skildum A, Pierson-Mullany L, Lange CA. 2005. Integration of progesterone receptor mediated rapid signaling and nuclear actions in breast cancer cell models: role of mitogen-activated protein kinases and cell cycle regulators. Steroids. 70(5-7):418-26.  

• Zhang P, Ostrander JH, Faivre EJ, Olsen A, Fitzsimmons D, Lange CA. 2005.  Regulated association of protein kinase B/Akt with breast tumor kinase. J Biol Chem. 280(3):1982-91.

• Pierson-Mullany LK, Lange CA. 2004. Phosphorylation of progesterone receptor serine 400 mediates ligand-independent transcriptional activity in response to activation of cyclin-dependent protein kinase 2.  Mol Cell Biol. 24(24):10542-57.  

• Lange CA. 2004. Making Sense of Cross-Talk Between Steroid Hormone Receptors and Intracellular Signaling Pathways: Who Will Have the Last Word? Mol Endo. 18(2):269-78.

• Pierson-Mullany, L, Skildum, A, Faivre, E, and Lange, CA. 2003. Cross-talk Between Growth Factor and Steroid Receptor Signaling Pathways: Implications for Breast Cancer Cell Growth. Breast Cancer, 18:21-31.

• Qiu, M and Lange, CA. 2003. MAP Kinases Couple Multiple Functions of Human Progesterone Receptors: Degradation, Transcriptional Synergy, and Nuclear Localization. J. Steroid Receptor Biochem. Mol. Biol. 85: 147-157.

• Qiu, M, Olsen, A, Faivre, E, Horwitz, KB, and Lange, CA. 2003. Mitogen Activated Protein Kinase Regulates Nuclear Association of Human Progesterone Receptors. Mol. Endo. 17: 628-642.

• Shen, T, Horwitz, KB, and Lange, CA. 2001. Transcriptional Hyper-Activity of Human Progesterone Receptors is Coupled to Their Ligand-Dependent Down-Regulation by Mitogen-Activated Protein Kinase-Dependent Phosphorylation of Serine 294. Mol. Cell. Biol. 21: 6122-6131.
  

 

Last modified on: July 13, 2010