Non-nuclear localization of Ki-67 in human colorectal cancer cells grown as multicellular layers

Yu Jin Kim, Sang Hoon Lee, Jaehwi Lee, Hyo Jeong Kuh

    Research output: Contribution to journalArticlepeer-review

    7 Citations (Scopus)

    Abstract

    Multicellular layers (MCL) of cancer cells is an in vitro 3-dimensional (3D) model that mimics avascular microregions of human solid tumors and has been shown to be useful in pharmacokinetic-pharmacodynamic studies of anticancer agents. We investigated whether Ki-67, which is widely used as a proliferation marker, can be used to evaluate changes in proliferative fractions following drug exposure in MCL of HT-29 human colorectal cancer cells. Ki-67 expression was monitored and compared between cancer cells cultured as monolayers or MCL. Drug distribution and Ki-67 expression were evaluated within MCL following exposure to doxorubicin and paclitaxel. Ki-67 expression was observed in the nuclei of proliferating cells in monolayers, tumor xenograft, and multicellular spheroids. In MCL, however, Ki-67 expression was detected in the membrane/cytoplasm as well as in the nucleus throughout MCL. Neither the location nor the level of expression changed following drug exposure, whereas drug-induced apoptosis increased. Our data show that membranous/cytoplasmic Ki-67 may not be valid as a marker for the proliferative activity of cells grown as MCL. Studies for non-nuclear localization and its mechanism in 3D in vitro models of other cell lines are warranted.

    Original languageEnglish
    Pages (from-to)634-640
    Number of pages7
    JournalArchives of pharmacal research
    Volume36
    Issue number5
    DOIs
    Publication statusPublished - 2013 May

    Bibliographical note

    Funding Information:
    Acknowledgments This work was supported by Mid-career Researcher Program through NRF Grant funded by the MEST (No. 2012R1A2A2A01003361) and the Nano-Biotechnology Project (Regenomics, 2011-0007745) of the Korean Science and Engineering Foundation (KOSEF). Yu-Jin Kim was sponsored by the Ministry of Knowledge Economy (MKE) and Korea Industrial Technology Foundation (KOTEF) through the Human Resource Training Project for Strategic Technology

    Copyright:
    Copyright 2013 Elsevier B.V., All rights reserved.

    Keywords

    • HT-29 human colorectal cancer cells
    • Ki-67
    • Multicellular layer
    • Multicellular spheroid
    • Proliferation marker
    • Three-dimensional culture

    ASJC Scopus subject areas

    • Molecular Medicine
    • Drug Discovery
    • Organic Chemistry

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