MICaB Graduate Program
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Carol A. Lange, Ph.D.
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:
- Girard BJ, Daniel AR, Lange CA, Ostrander JH. 2013. PELP1: A review of PELP1 interactions, signaling, and biology. Mol Cell Endocrinol.
- Regan Anderson TM, Peacock DL, Daniel AR, Hubbard GK, Lofgren KA, Girard BJ, Schörg A, Hoogewijs D, Wenger RH, Seagroves TN, Lange CA. 2013. Breast Tumor Kinase (Brk/PTK6) Is a Mediator of Hypoxia-Associated Breast Cancer Progression. Cancer Res. Sep 15;73(18):5810-20.
- Hagan CR, Knutson TP, Lange CA. 2013. A Common Docking Domain in Progesterone Receptor-B links DUSP6 and CK2 signaling to proliferative transcriptional programs in breast cancer cells. Nucleic Acids Res.
- Knutson TP, Lange CA. 2013. Dynamic regulation of steroid hormone receptor transcriptional activity by reversible SUMOylation. Vitam Horm.;93:227-61.
- Diep CH, Charles NJ, Gilks CB, Kalloger SE, Argenta PA, Lange CA. 2013. Progesterone receptors induce FOXO1-dependent senescence in ovarian cancer cells. Cell Cycle. 12(9):1433-49.
- Knutson TP, Daniel AR, Fan D, Silverstein KA, Covington KR, Fuqua SA, Lange CA. 2012. Phosphorylated and sumoylation-deficient progesterone receptors drive proliferative gene signatures during breast cancer progression. Breast Cancer Res. 14(3):R95.
- Locatelli A, Lofgren KA, Daniel AR, Castro NE, Lange CA. 2012. Mechanisms of HGF/Met signaling to Brk and Sam68 in breast cancer progression. Horm Cancer. 3(1-2):14-25.
- Hagan CR, Daniel AR, Dressing GE, Lange CA. 2012. Role of phosphorylation in progesterone receptor signaling and specificity.Mol Cell Endocrinol.357(1-2):43-9.
- Lofgren KA, Ostrander JH, Housa D, Hubbard GK, Locatelli A, Bliss RL, Schwertfeger KL, Lange CA. 2011. Mammary gland specific expression of Brk/PTK6 promotes delayed involution and tumor formation associated with activation of p38 MAPK. Breast Cancer Res. 13(5):R89.
- Daniel AR, Hagan CR, Lange CA. 2011. Progesterone receptor action: defining a role in breast cancer. Expert Rev Endocrinol Metab. ;6(3):359-369.
- Lange CA, Yee D. 2011. Killing the second messenger: targeting loss of cell cycle control in endocrine-resistant breast cancer. Endocr Relat Cancer.18(4):C19-24.
- Hagan CR, Regan TM, Dressing GE, Lange CA. 2011. ck2-dependent phosphorylation of progesterone receptors (PR) on Ser81 regulates PR-B isoform-specific target gene expression in breast cancer cells. Mol Cell Biol.31(12):2439-52.
- Locatelli A, Lange CA. 2011. Met receptors induce Sam68-dependent cell migration by activation of alternate extracellular signal-regulated kinase family members. J Biol Chem. 286(24):21062-72.
- Dressing GE, Goldberg JE, Charles NJ, Schwertfeger KL, Lange CA. 2011. Membrane progesterone receptor expression in mammalian tissues: a review of regulation and physiological implications. Steroids. 76(1-2):11-7.
- Daniel AR, Gaviglio AL, Czaplicki LM, Hillard CJ, Housa D, Lange CA. 2010. The progesterone receptor hinge region regulates the kinetics of transcriptional responses through acetylation, phosphorylation, and nuclear retention. Mol Endocrinol 24(11):2126-38
- Castro NE, Lange CA. 2010. Breast tumor kinase and extracellular signal-regulated kinase 5 mediate Met receptor signaling to cell migration in breast cancer cells. Breast Cancer Res.12(4):R60.
- Charles NJ, Thomas P, Lange CA. 2010. Expression of membrane progesterone receptors (mPR/PAQR) in ovarian cancer cells: implications for progesterone-induced signaling events. Horm Cancer.;1(4):167-76.
- 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 review)