Abstract
In order to better understand how tumor cells develop resistance to chemotherapy drugs, we screened a human cDNA expression library in Jurkat cells for cDNA's that conferred resistance to doxorubicin-induced cell death. One of the cDNA's isolated in the screen codes for ribosomal protein L35a, a component of the large subunit of the ribosome. Jurkat cells engineered to overexpress L35a protein were more resistant not only to doxorubicin but also to UV-irradiation, anti-Fas antibody, and serum starvation compared to Jurkat cells expressing endogenous levels of L35a. Jurkat cells overexpressing L35a did not have increased levels of the anti-apoptotic proteins Bcl-2 or Bcl-xL, the drug efflux pump P-glycoprotein, nor altered cellular growth kinetics or total protein synthesis. Our results provide new insight into L35a function and suggest that it may have a role in the cellular response to cytotoxic damage. Since L35a RNA is overexpressed in a significant number of glioblastoma multiforme (GBM) brain tumors, our results may stimulate further investigation into the possible role of L35a in the resistance of GBM to cytotoxic therapy.
Original language | English (US) |
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Pages (from-to) | 195-202 |
Number of pages | 8 |
Journal | Cancer Letters |
Volume | 180 |
Issue number | 2 |
DOIs | |
State | Published - Jun 28 2002 |
Keywords
- Chemotherapy resistance
- Glioblastoma multiforme
- Jurkat
- L35a
- Ribosomal protein
ASJC Scopus subject areas
- Oncology
- Cancer Research