Rina Plattner, Ph.D.
Associate Professor
Indiana University, 1992
Office: 209 Combs Cancer Research Building (0096)
Lab: (859) 323-5529
Tel: (859) 323-4778
The Abl family of non-receptor tyrosine kinases (c-Abl, Arg) is extremely important in the development of human leukemia as c-Abl is translocated next to the BCR gene (t(9;22)) in greater than 95% of patients with chronic myelogenous leukemia (CML). The resulting fusion protein (BCR-Abl) has constitutively active tyrosine kinase activity, and transforms hematopoietic cells by decreasing cellular adhesion, and increasing proliferation and migration. An Abl kinase inhibitor (Gleevec) is now an FDA-approved treatment for BCR-Abl+ CML. Unlike leukemia, the Abl genes are not translocated in solid tumors, and therefore were thought not to have a role in their development or progression. However, we were the first to show that Abl kinases are activated in invasive breast cancer and melanoma cell lines by a novel mechanism (ie. downstream of deregulated receptor tyrosine kinases and Src kinases). Significantly, we showed that Abl kinases are required for invasion, proliferation, anchorage-independent growth, survival in response to nutrient deprivation, and metastasis. Therefore, our current studies are aimed at understanding the mechanisms by which Abl kinases promote these processes, as well as determining the mechanisms by which Abl kinase inhibitors sensitize breast cancers and melanomas containing active Abl kinases to chemotherapeutic agents. We also are testing whether c-Abl inhibitors cooperate with targeted agents that target c-Abl/Arg-independent pathways to kill melanoma and breast cancer cells.
Selected Publications
Srinivasan, D., and R. Plattner (2006).
Activation of Abl tyrosine kinases promotes invasion of aggressive breast cancer cells.
Cancer Res. 66(11):5648-5655. PMID: 16740702
Srinivasan, D., Sims, J.T., Plattner R. (2007)
Deregulated Abl kinases promote proliferation, anchorage-independent growth and survival of aggressive breast cancer cells.
Oncogene. 2008 Feb 14;27(8):1095-105. Epub 2007 Aug 13. PMID: 17700528
Mitra, S, Beach,C, Feng G.S., Plattner. R. (2008).
SHP-2 is a novel target of Abl kinases during cell proliferation.
J. Cell Science 121:3335-3346. PMID: 18827006
Srinivasan, D., Kaetzel, D.M., Plattner, R. (2009).
Reciprocal regulation of Abl kinases and PDGFR-β.
Cellular Signaling 21(7):1143-50. PMID: 19275932
Sims, J.T., and R. Plattner. (2009)
MTT assays cannot be utilized to study the effects of STI571/Gleevec on the viability of solid tumor cell lines.
Cancer Chemotherapy and Pharmacology 64(3):629. PMID: 19396599
Sims, J.T., Fiore, L, Ganguly, S., Holler, C., Park, E.S., Plattner, R. (2009).
STI571 (Gleevec) sensitizes breast cancer cells to 5-Fluorouracil, Cisplatin, and Camptothecin in a cell-type specific manner.
Biochemical Pharmacology 78(3):249-60. PMID: 19427998
Ganguly, SS, Fiore, LS, Sims JT, Friend JW, Srinivasan D, Cibull ML, Wang Ch, Novak M., Kaetzel, DM, Plattner, R. (2011).
c-Abl and Arg are activated in human primary melanomas, promote melanoma cell invasion via distinct pathways, and drive metastatic progression.
Oncogene doi:10.1038/onc.2011.361.
Disclaimer: Journal articles can be downloaded from this site for personal use only and may not be duplicated or distributed for commercial reasons, without written authorization from the Journal, the copyright holder.