title: Involvement of insulin-like growth factor-I secretion and all-trans-retinoic acid-induced decrement in viability in MCF-7 cells.
abstract: OBJECTIVE
  Insulin-like growth factor-I (IGF-I) is associated with survival, apoptosis and proliferation in MCF-7 cells. All-trans-retinoic acid (RA) is used as a cancer therapeutic, but the use of RA in cancer therapy is limited by the unpredictable resistance of cancer cells to drug action. Furthermore, the relationship of IGF-I with RA-induced decrement in cell viability has yet to be elucidated.
  
  
  METHODS
  MCF-7 cells were grown as confluent monolayers. To demonstrate the signaling pathways and roles of IGF-I, we suppressed endogenous target IGF-I with specific small interfering RNA treatment. Protein kinase C-δ and insulin receptor substrate 1 (IRS-1) protein levels were analyzed by Western blot. Radioimmunoassays were used to assess the concentration of endogenous IGF-I, and RT-PCR was used to assess IGF-I mRNA expression. Cell viability was analyzed with the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay.
  
  
  RESULTS
  We showed that RA treatment resulted in a dose- and time-dependent decrease in the secretion and synthesis of IGF-I. Subsequently, we found that suppression of IGF-I and IRS-1 protein decreased cell viability. In contrast, suppression of protein kinase C-δ and stimulation of IGF-I protected cells from RA-induced decrement in cell viability. The combination of RA treatment with IGF-I or IRS-1 small interfering RNA resulted in an additive decrease in cell viability.
  
  
  CONCLUSIONS
  These results indicate that IGF-I plays an important role in the effect of RA and that suppression of IGF-I is implicated in the RA-induced inhibition of cell viability in MCF-7 cells.
authors.affiliation: Department of Veterinary Physiology, College of Veterinary Medicine, Bio-Safety Research Institute, Chonbuk National University, Jeonju, Republic of Korea.
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Oh
authors.forename: Jong-Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Chang-Won
authors.initials: CW
authors.lastname: Kang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D051745:Protein Kinase C-delta / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D055504:Insulin Receptor Substrate Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014212:Tretinoin; D007334:Insulin-Like Growth Factor I; D051745:Protein Kinase C-delta