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CRBP suppresses breast cancer cell survival and anchorage-independent growth

Oncogene volume 20, pages 7413–7419 (2001)Cite this article

Abstract

We showed earlier that cellular retinol-binding protein (CRBP) expression is downregulated in a subset of human breast cancers. We have now investigated the outcome of ectopic CRBP expression in MTSV1-7 cells, a SV40 T antigen-transformed human breast epithelial cell line devoid of endogenous CRBP expression. We found that: (i) CRBP did not inhibit adherent cell growth but suppressed foci formation in post-confluent cultures and colony formation in soft agar; (ii) this effect was due to CRBP inhibition of cell survival, as demonstrated by viability and TUNEL assays of cells in soft-agar or plated on polyHEMA-coated dishes; (iii) CRBP inhibited protein kinase B/Akt activation in cells in suspension but not in adherent cells and the CRBP suppression of anchorage-independent growth was mimicked by cell treatment with the phosphatidylinositol-3 kinase (PI3K) inhibitor LY294002; (iv) CRBP enhanced retinyl ester formation and storage but did not regulate retinoic acid synthesis or retinoic acid receptor activity. Ectopic CRBP-mediated inhibition of anchorage-independent cell survival and colony formation in the absence of significantly altered responses to either retinol or retinoic acid was also documented in T47D human breast cancer cells. In conclusion, the data suggest two novel and linked CRBP functions in mammary epithelial cells: inhibition of the PI3K/Akt survival pathway and suppression of anchorage-independent growth.

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Acknowledgements

We thank Joyce Taylor-Papadimitriou (MTSV1-7 cells), Pierre Chambon (pSG5.mCRBP) and M Klaus (Ro 41-5253) for reagent gifts; Dave Ong for sharing his laboratory for the HPLC analyses; Scott Henderson and Vladimir Protopopov for the electron microscopy; Yongkui Jing for his initial contribution to this study; and Eduardo Farias and Liliana Ossowski for helpful discussions. This work was supported by NIH grant CA54273, The Samuel Waxman Cancer Research Foundation and The Norman and Rosita Winston Foundation; Brent Rexer was supported by NIH grants R01DK32642 and 5T32HD07043 to David Ong.

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Authors and Affiliations

  1. Department of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029-6574, USA

    Yuvarani S Kuppumbatti & Rafael Mira-y-Lopez

  2. Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, Tennessee, USA

    Brent Rexer

  3. Laboratory of Biological Chemistry, School of Pharmaceutical Sciences, Showa University, Japan

    Shigeo Nakajo & Kazuyasu Nakaya

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  1. Yuvarani S Kuppumbatti
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  2. Brent Rexer
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  5. Rafael Mira-y-Lopez
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Correspondence to Yuvarani S Kuppumbatti or Rafael Mira-y-Lopez.

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Kuppumbatti, Y., Rexer, B., Nakajo, S. et al. CRBP suppresses breast cancer cell survival and anchorage-independent growth. Oncogene 20, 7413–7419 (2001). https://doi.org/10.1038/sj.onc.1204749

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