Transfer of p14ARF gene in drug-resistant human breast cancer MCF-7/Adr cells inhibits proliferation and reduces doxorubicin resistance.
The INK4a/ARF locus on human chromosome 9p21 encodes two tumor suppressors, p16INK4a and p14ARF, that restrain cell growth by affecting the functions of the retinoblastoma protein and p53, respectively. Overexpression of ARF results in cell cycle arrest in both G1 and G2. To elucidate the effect of p14ARF gene on multidrug-resistant tumor cells, we transferred a p14ARF cDNA into p53-mutated MCF-7/Adr human breast cancer cells. In this report we demonstrated for the first time that p14ARF expression was able to greatly inhibit the MCF-7/Adr cell proliferation. Furthermore, p14ARF expression resulted in decrease of MDR-1 mRNA and P-glycoprotein production, which linked to the reducing resistance of MCF-7/Adr cells to doxorubicin. These results imply that drug resistance might be effectively reversed by the wild-type p14ARF expression in human breast cancer cells.
Guo-Chang
F
F
Department of Experimental Hematology, Beijing Institute of Radiation Medicine, 27 Tai Ping Road, 100850, PR, Beijing, China.
Chu-Tse
W
W
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects* / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D006801:Humans; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D025803:Tumor Suppressor Protein p14ARF
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D011506:Proteins; D012333:RNA, Messenger; D025803:Tumor Suppressor Protein p14ARF; D004317:Doxorubicin