Cloning of a novel human RNA polymerase II subunit downregulated by doxorubicin: new potential mechanisms of drug related toxicity.
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.
Fanciulli
M
M
Cell Metabolism and Pharmacokinetics Laboratory, Regina Elena Cancer Institute, Rome, Italy.
Bruno
T
T
Cerboni
C
C
Bonetto
F
F
Iacobini
C
C
Frati
L
L
Piccoli
M
M
Floridi
A
A
Santoni
A
A
Punturieri
A
A
D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D001943:Breast Neoplasms; D002460:Cell Line; D003001:Cloning, Molecular / Q000187:drug effects*; D003110:Colonic Neoplasms; D017124:Conserved Sequence; D017931:DNA Primers; D018076:DNA, Complementary; D004317:Doxorubicin / Q000494:pharmacology* / Q000633:toxicity; D019008:Drug Resistance, Neoplasm; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012319:RNA Polymerase II / Q000096:biosynthesis* / Q000737:chemistry; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D018076:DNA, Complementary; D046911:Macromolecular Substances; D012333:RNA, Messenger; D011994:Recombinant Proteins; D004317:Doxorubicin; D012319:RNA Polymerase II