title: CRBP suppresses breast cancer cell survival and anchorage-independent growth.
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.
authors.affiliation: Department of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029-6574, USA. kuppuy01@doc.mssm.edu
authors.forename: Y S
authors.initials: YS
authors.lastname: Kuppumbatti
authors.forename: B
authors.initials: B
authors.lastname: Rexer
authors.forename: S
authors.initials: S
authors.lastname: Nakajo
authors.forename: K
authors.initials: K
authors.lastname: Nakaya
authors.forename: R
authors.initials: R
authors.lastname: Mira-y-Lopez
mesh_terms: D000362:Agar; D017209:Apoptosis / Q000187:drug effects*; D001940:Breast / Q000166:cytology; D001943:Breast Neoplasms / Q000473:pathology*; D002352:Carrier Proteins / Q000378:metabolism; D002448:Cell Adhesion; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D002867:Chromones / Q000494:pharmacology; D003260:Contact Inhibition; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005260:Female; D006801:Humans; D009025:Morpholines / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D012177:Retinol-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology*; D054840:Retinol-Binding Proteins, Cellular; D015398:Signal Transduction / Q000187:drug effects; D013539:Simian virus 40 / Q000502:physiology; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology; D014410:Tumor Stem Cell Assay; D025521:Tumor Suppressor Proteins; D014801:Vitamin A / Q000494:pharmacology
chemical_list: D000362:Agar; D002352:Carrier Proteins; D002867:Chromones; D004791:Enzyme Inhibitors; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D009025:Morpholines; D009363:Neoplasm Proteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D018168:Receptors, Retinoic Acid; D012177:Retinol-Binding Proteins; D054840:Retinol-Binding Proteins, Cellular; D014212:Tretinoin; D025521:Tumor Suppressor Proteins; D014801:Vitamin A; C107608:FABP7 protein, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C494918:AKT1 protein, human