Biotech Values

[Preciouslife1]

Cancer Cell Biology

http://www3.interscience.wiley.com/cgi-bin/abstract/116322118/ABSTRACT?CRETRY=1&SRETRY=0

Erythropoietin treatment of human ovarian cancer cells results in enhanced signaling and a paclitaxel-resistant phenotype.

Peter Solar, Laurie Feldman, Jee-Yeong Jeong, Jacqueline R. Busingye, Arthur J. Sytkowski *
Laboratory for Cell and Molecular Biology, Division of Hematology and Oncology, Beth Israel Deaconess Medical Center,Department of Medicine, Harvard Medical School, Boston, MA

email: Arthur J. Sytkowski ([e-mail])

*Correspondence to Arthur J. Sytkowski, Laboratory for Cell and Molecular Biology, Beth Israel Deaconess Medical Center, 330 Brookline Ave. - W/BL 548, Boston, MA 02215, USA

Fax: [phone] or [phone].

Funded by:
NIH; Grant Number: R01 CA 89204
DOD; Grant Number: DAMD17-03-1-0233
Slovak Science and Technology Assistance Agency; Grant Number: APVT-20-012104, VEGA No. 1/3253/06
Elsa U. Pardee Foundation and the Gustave and Louise Pfeiffer Research Foundation
DNAPrint Pharmaceuticals

Keywords
erythropoietin • signaling • ovarian cancer • paclitaxel • chemoresistance • apoptosis


Abstract
Erythropoietin (Epo), a glycoprotein hormone that is the principal regulator of erythropoiesis, is known to act also on nonhematopoietic cell types. Epo receptors have been reported on several normal and neoplastic human cells and tissues, including ovarian cancer cells. We found that long-term Epo treatment of A2780 cells resulted in the development of a phenotype exhibiting both enhanced Epo signaling, evidenced by increased peak levels of phospho-Erk1/2 and increased paclitaxel resistance. This phenotypic effect was specific for paclitaxel, since no change in cisplatin or carboplatin sensitivity was observed. In addition, the change in phenotype was stable, even after the removal of Epo. Measurement of mono- and oligonucleosome formation revealed that long-term Epo treated A2780 cells exhibited markedly less apoptosis than nonerythropoietin treated cells at essentially all concentrations of paclitaxel tested. Western blot analyses revealed that the long-term Epo treated cells had significantly reduced expression of apoptosis-related proteins Bcl-2 and Bcl-10. These findings may have implications for the clinical use of recombinant human Epo and other erythropoiesis stimulating agents to correct anemia in paclitaxel-treated cancer patients. © 2007 Wiley-Liss, Inc.