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Article

Increased chemoresistance to paclitaxel in the MCF10AT series of human breast epithelial cancer cells

  • Authors:
    • Soo-Jeong Lim
    • Hyeon Gyeom Choi
    • Chae Kyung Jeon
    • So Hee Kim
  • View Affiliations / Copyright

    Affiliations: Department of Bioscience and Biotechnology, Sejong University, Seoul, Republic of Korea, College of Natural Science, Hannam University, Daejeon, Republic of Korea, Grinnell College, Grinnell, IA, USA, College of Pharmacy and Research Institute of Pharmaceutical Science and Technology, Ajou University, Suwon, Republic of Korea
  • Pages: 2023-2030
    |
    Published online on: February 2, 2015
       https://doi.org/10.3892/or.2015.3775
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Abstract

The MCF10AT cell series of human breast epithelial cancer cells includes normal MCF10A (10A), premalignant MCF10AT (10AT) and MCF10ATG3B (10ATG3B), and fully malignant MCF10CA1a (10CA1a) cells. The series is a unique model system showing progressive tumorigenic potential with the same origin. The effects of paclitaxel, a microtubule inhibitor, were evaluated in this cell system. Paclitaxel inhibited cell proliferation in a time-dependent (24, 48 and 72 h) and concentration-dependent (0-10 nM) manners with less sensitivity in 10CA1a cells. Treatment with paclitaxel (10 nM) for 24 h induced apoptosis in 10A, 10AT, 10ATG3B and 10CA1a cells, with 23.6, 26.1, 25.2 and 8.96%, respectively, in the sub-G1 phase. Treatment with paclitaxel (0-10 nM) for 24 h, resulted in the appearance of DNA fragmentation (a hallmark of apoptosis) with less sensitivity in the 10CA1a tumor cells. Paclitaxel increased p53 protein expression in 10A, 10AT, 10ATG3B and 10CA1a cells, by 87, 102, 812 and 84%, respectively. The p21Waf1/Cip1 protein expression increased by 2.57-, 1.53- and 2.48-fold in 10A, 10AT and 10ATG3B cells, respectively, with negligible detection in the 10CA1a cells. Activation of the Akt signaling pathway was observed in the MCF10AT cell lineage and the protein expression of phospho-Akt (Ser473 and Thr308). The downstream targets of this pathway, phospho-p70S6K and phospho-S6RP, were also inhibited by paclitaxel in 10A, 10AT and 10ATG3B cells, but minimally inhibited in 10CA1a cells, suggestive of chemoresistance in 10CA1a cells. The effects of paclitaxel on the multidrug resistance 1 (MDR1), MRP1 and breast cancer resistance protein (BCRP) gene expression were not significant in the MCF10AT cell lineage. These results collectively indicated that paclitaxel inhibited cell proliferation and induced apoptosis in the MCF10AT cell lineage, with chemoresistance in 10CA1a tumor cells. The decreased responsiveness to paclitaxel observed in 10CA1a tumor cells was likely due, in part, to activation of the Akt signaling pathway and a high expression of wild-type p53 with lack of p21Waf1/Cip1.
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Copy and paste a formatted citation
Spandidos Publications style
Lim S, Choi HG, Jeon CK and Kim SH: Increased chemoresistance to paclitaxel in the MCF10AT series of human breast epithelial cancer cells. Oncol Rep 33: 2023-2030, 2015.
APA
Lim, S., Choi, H.G., Jeon, C.K., & Kim, S.H. (2015). Increased chemoresistance to paclitaxel in the MCF10AT series of human breast epithelial cancer cells. Oncology Reports, 33, 2023-2030. https://doi.org/10.3892/or.2015.3775
MLA
Lim, S., Choi, H. G., Jeon, C. K., Kim, S. H."Increased chemoresistance to paclitaxel in the MCF10AT series of human breast epithelial cancer cells". Oncology Reports 33.4 (2015): 2023-2030.
Chicago
Lim, S., Choi, H. G., Jeon, C. K., Kim, S. H."Increased chemoresistance to paclitaxel in the MCF10AT series of human breast epithelial cancer cells". Oncology Reports 33, no. 4 (2015): 2023-2030. https://doi.org/10.3892/or.2015.3775
Copy and paste a formatted citation
x
Spandidos Publications style
Lim S, Choi HG, Jeon CK and Kim SH: Increased chemoresistance to paclitaxel in the MCF10AT series of human breast epithelial cancer cells. Oncol Rep 33: 2023-2030, 2015.
APA
Lim, S., Choi, H.G., Jeon, C.K., & Kim, S.H. (2015). Increased chemoresistance to paclitaxel in the MCF10AT series of human breast epithelial cancer cells. Oncology Reports, 33, 2023-2030. https://doi.org/10.3892/or.2015.3775
MLA
Lim, S., Choi, H. G., Jeon, C. K., Kim, S. H."Increased chemoresistance to paclitaxel in the MCF10AT series of human breast epithelial cancer cells". Oncology Reports 33.4 (2015): 2023-2030.
Chicago
Lim, S., Choi, H. G., Jeon, C. K., Kim, S. H."Increased chemoresistance to paclitaxel in the MCF10AT series of human breast epithelial cancer cells". Oncology Reports 33, no. 4 (2015): 2023-2030. https://doi.org/10.3892/or.2015.3775
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