Key result
Doxorubicin treatment downregulated the mRNA and protein expression of the human homologue of the RPB11 subunit of RNA polymerase II in human cell lines.
Why the study?
Does doxorubicin treatment downregulate the expression of the RNA polymerase II subunit RPB11 in human cell lines?
Does doxorubicin treatment downregulate the expression of the RNA polymerase II subunit RPB11 in human cell lines?
The downregulation of the highly heart-expressed RNA polymerase II subunit RPB11 by doxorubicin provides a potential novel molecular mechanism for its cardiotoxicity.
May implicate RPB11 in doxorubicin cardiotoxicity; leaves open in vivo relevance.
Using the differential display PCR method, we have isolated an mRNA downregulated in doxorubicin resistant human cell lines. The full length cDNA clone was identified as the human homologue of yeast RPB11 subunit of RNA polymerase II. Northern blot analysis of normal tissues detected a particularly high expression of RPB11 mRNA in heart and skeletal muscle. Reduction of this mRNA expression was observed in all the cell lines tested after drug treatment and was paralleled by a similar decrease of the protein levels. These findings suggest that doxorubicin may exert in vivo specific inhibitory effects on a major component of the transcription machinery.
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Fanciulli et al. (1996) studied Doxorubicin toxicity. Doxorubicin was evaluated on RPB11 mRNA and protein expression. Doxorubicin treatment downregulated the mRNA and protein expression of the human homologue of the RPB11 subunit of RNA polymerase II in human cell lines.
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