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  • Hilvo, MikaBio and Process Technology, VTT Technical Research Centre of Finland, Espoo, Finland (author)

Novel theranostic opportunities offered by characterization of altered membrane lipid metabolism in breast cancer progression

  • Article/chapterEnglish2011

Publisher, publication year, extent ...

  • Philadelphia, PA, USA :American Association for Cancer Research,2011
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:oru-59353
  • https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-59353URI
  • https://doi.org/10.1158/0008-5472.CAN-10-3894DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Activation of lipid metabolism is an early event in carcinogenesis and a central hallmark of many cancers. However, the precise molecular composition of lipids in tumors remains generally poorly characterized. The aim of the present study was to analyze the global lipid profiles of breast cancer, integrate the results to protein expression, and validate the findings by functional experiments. Comprehensive lipidomics was conducted in 267 human breast tissues using ultraperformance liquid chromatography/ mass spectrometry. The products of de novo fatty acid synthesis incorporated into membrane phospholipids, such as palmitate-containing phosphatidylcholines, were increased in tumors as compared with normal breast tissues. These lipids were associated with cancer progression and patient survival, as their concentration was highest in estrogen receptor-negative and grade 3 tumors. In silico transcriptomics database was utilized in investigating the expression of lipid metabolism related genes in breast cancer, and on the basis of these results, the expression of specific proteins was studied by immunohistochemistry. Immunohistochemical analyses showed that several genes regulating lipid metabolism were highly expressed in clinical breast cancer samples and supported also the lipidomics results. Gene silencing experiments with seven genes [ACACA (acetyl-CoA carboxylase α), ELOVL1 (elongation of very long chain fatty acid-like 1), FASN (fatty acid synthase), INSIG1 (insulin-induced gene 1), SCAP (sterol regulatory element-binding protein cleavage-activating protein), SCD (stearoyl-CoA desaturase), and THRSP (thyroid hormone-responsive protein)] indicated that silencing of multiple lipid metabolism-regulating genes reduced the lipidomic profiles and viability of the breast cancer cells. Taken together, our results imply that phospholipids may have diagnostic potential as well as that modulation of their metabolism may provide therapeutic opportunities in breast cancer treatment.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Denkert, CarstenInstitute of Pathology, Berlin, Germany (author)
  • Lehtinen, LauraBio and Process Technology, VTT Technical Research Centre of Finland, Turku, Finland (author)
  • Müller, BeritInstitute of Pathology, Berlin, Germany (author)
  • Brockmöller, ScarletInstitute of Pathology, Berlin, Germany (author)
  • Seppänen-Laakso, TuulikkiBio and Process Technology, VTT Technical Research Centre of Finland, Espoo, Finland (author)
  • Budczies, JanInstitute of Pathology, Berlin, Germany (author)
  • Bucher, ElmarBio and Process Technology, VTT Technical Research Centre of Finland, Turku, Finland (author)
  • Yetukuri, LaxmanBio and Process Technology, VTT Technical Research Centre of Finland, Espoo, Finland (author)
  • Castillo, SandraBio and Process Technology, VTT Technical Research Centre of Finland, Espoo, Finland (author)
  • Berg, EmiliaBio and Process Technology, VTT Technical Research Centre of Finland, Espoo, Finland (author)
  • Nygren, HeliBio and Process Technology, VTT Technical Research Centre of Finland, Espoo, Finland (author)
  • Sysi-Aho, MarkoBio and Process Technology, VTT Technical Research Centre of Finland, Espoo, Finland (author)
  • Griffin, Julian L.Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom (author)
  • Fiehn, OliverGenome Center, University of California, Davis CA, United States (author)
  • Loibl, SibylleGerman Breast Group, GBG-Forschungs GmbH, Neu-Isenburg, Germany (author)
  • Richter-Ehrenstein, ChristianecBreast Cancer Center, Charité University Hospital, Berlin, Germany (author)
  • Radke, CorneliaInstitute of Pathology, DRK Klinikum Berlin Köpenick, Berlin, Germany (author)
  • Hyötyläinen, Tuulia,1971-Örebro universitet,Institutionen för naturvetenskap och teknik,Bio and Process Technology, VTT Technical Research Centre of Finland, Espoo, Finland(Swepub:oru)tihn (author)
  • Kallioniemi, OlliBio and Process Technology, VTT Technical Research Centre of Finland, Turku, Finland (author)
  • Iljin, KristiinaBio and Process Technology, VTT Technical Research Centre of Finland, Turku, Finland (author)
  • Oresic, Matej,1967-Bio and Process Technology, VTT Technical Research Centre of Finland, Espoo, Finland(Swepub:oru)moc (author)
  • Bio and Process Technology, VTT Technical Research Centre of Finland, Espoo, FinlandInstitute of Pathology, Berlin, Germany (creator_code:org_t)

Related titles

  • In:Cancer ResearchPhiladelphia, PA, USA : American Association for Cancer Research71:9, s. 3236-450008-54721538-7445

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