Rina Plattner, Ph.D.
Assistant Professor
Indiana University, 1992
Office: 209 Combs Cancer Research Building (0096)
Lab: (859) 323-5529
Tel: (859) 323-4778
Our laboratory is focused on the study of the Abelson family of proteins (c-Abl, Arg), a class of proteins that are linked to the development of human leukemia. c-Abl is translocated next to the BCR gene (t(9;22)) in more than 95% of patients with chronic myelogenous leukemia (CML). This translocation produces a constitutively active Abl protein. In addition to producing leukemia in humans, constitutively active Abl proteins also transform a variety of cell types in the laboratory. Recently Gleevec, an inhibitor of the Abelson kinases, was approved for the treatment of patients with CML. Gleevec is one of the initial "smart drugs", a new generation of chemotherapeutic drugs developed to combat abnormally regulated proteins in cancer cells. Gleevec is effective in inducing remission in early stage CML patients, and produces fewer side effects than conventional chemotherapy. However, Gleevec is less effective in patients with advanced disease due to drug resistance. Although Abl proteins have been linked to the development of leukemia, their normal cellular functions are not well understood. Our laboratory is focusing on understanding the normal function of the Abl family of proteins. We found that the activity of the Abl family of proteins is increased by growth factor stimulation of fibroblasts. Growth factors, such as platelet-derived growth factor (PDGF), induce cell proliferation, differentiation, migration, and survival, events that must be tightly controlled in order to prevent disease states, such as cancer. We also found that the Abl kinases play an important role in proliferation and migration downstream of the PDGF signal in fibroblasts. Current projects in the laboratory involve dissecting the mechanism by which the Abl kinases regulate cellular proliferation and migration downstream of growth factor signals (signal transduction), as well as determining whether the Abl kinases play important roles in cancers other than leukemia. Unraveling signal transduction pathways involving the Abl proteins may aid in the discovery of new drug targets for treating patients with solid tumors or CML patients with Gleevec resistance.
Selected Publications
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Srinivasan D, and Plattner R. (2006)
Activation of abl tyrosine kinases promotes invasion of aggressive breast cancer cells. Cancer Res. Jun 1;66(11):5648-5655.
Plattner, R. Koleske, A.J., Kazlauskas, A., Pendergast, A.M. (2004)
Bidirectional signaling links the Ableson kinases to the PDGF receptors.
Mol Cell Biol 24:2573-2583.
Plattner, R. and Pendergast, A.M. (2003)
Extra Views. Activation and Signaling of the Abl Tyrosine Kinase: Bidirectional Link with Phosphoinositide Signaling.
Cell Cycle 2:A8-9.
Plattner, R., Irvin, B.J., Guo, S., Blackburn, K., Kazlauskas, A., Abraham, R.T., York, J.D., Pendergast, A.M. (2003)
A New Link Between the c-Abl Tyrosine Kinase and Phosphoinositide Signaling via PLC-g1.
Nature Cell Biology 5:309-319.
Plattner, R., Kadlec, L., DeMali, K.A., Kazlauskas, A., Pendergast, A.M. (1999).
c-Abl is activated by growth factors and Src family kinases and has a role in the cellular response to PDGF.
Genes & Development 13, 2400-2411.
Plattner, R., Khosravi-Far, R., Sato, K.Y., Perucho, M., Der, C.J., Stanbridge, E.J. (1999).
Differential contribution of the ERK and JNK mitogen-activated protein kinase cascades to Ras transformation of HT1080 fibrosarcoma and
DLD-1 colon carcinoma cells.
Oncogene 18:1807-1817.
Plattner, R., Anderson, M.J., Sato, K.Y., Fasching, C.L., Der, C.J., Stanbridge, E.J. (1996).
Loss of oncogenic ras expression does not correlate with loss of tumorigenicity in human cells.
Proc. Natl. Acad. Sci. USA 93:6665-6670.
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