CRBP suppresses breast cancer cell survival and anchorage-independent growth.

Kuppumbatti YS, Rexer B, Nakajo S, Nakaya K, Mira-y-Lopez R
Oncogene. 2001 20 (50): 7413-9

PMID: 11704871 · DOI:10.1038/sj.onc.1204749

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.

MeSH Terms (33)

Agar Apoptosis Breast Breast Neoplasms Carrier Proteins Cell Adhesion Cell Division Cell Line, Transformed Cell Transformation, Viral Chromones Contact Inhibition Enzyme Activation Enzyme Inhibitors Fatty Acid-Binding Protein 7 Fatty Acid-Binding Proteins Female Humans Morpholines Neoplasm Proteins Phosphatidylinositol 3-Kinases Phosphoinositide-3 Kinase Inhibitors Protein-Serine-Threonine Kinases Proto-Oncogene Proteins Proto-Oncogene Proteins c-akt Receptors, Retinoic Acid Retinol-Binding Proteins Retinol-Binding Proteins, Cellular Signal Transduction Simian virus 40 Tretinoin Tumor Stem Cell Assay Tumor Suppressor Proteins Vitamin A

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