title: Intratumor cholesteryl ester accumulation is associated with human breast cancer proliferation and aggressive potential: a molecular and clinicopathological study.
abstract: BACKGROUND
  The metabolic effect of intratumor cholesteryl ester (CE) in breast cancer remains poorly understood. The objective was to analyze the relationship between intratumor CE content and clinicopathological variables in human breast carcinomas.
  
  
  METHODS
  We classified 30 breast carcinoma samples into three subgroups: 10 luminal-A tumors (ER+/PR+/Her2-), 10 Her-2 tumors (ER-/PR-/Her2+), and 10 triple negative (TN) tumors (ER-/PR-/Her2-). We analyzed intratumor neutral CE, free cholesterol (FC) and triglyceride (TG) content by thin layer chromatography after lipid extraction. RNA and protein levels of lipid metabolism and invasion mediators were analyzed by real time PCR and Western blot analysis.
  
  
  RESULTS
  Group-wise comparisons, linear regression and logistic regression models showed a close association between CE-rich tumors and higher histologic grade, Ki-67 and tumor necrosis. CE-rich tumors displayed higher mRNA and protein levels of low-density lipoprotein receptor (LDLR) and scavenger receptor class B member 1 (SCARB1). An increased expression of acetyl-Coenzyme A acetyltransferase 1 (ACAT1) in CE-rich tumors was also reported.
  
  
  CONCLUSIONS
  Intratumor CE accumulation is intimately linked to proliferation and aggressive potential of breast cancer tumors. Our data support the link between intratumor CE content and poor clinical outcome and open the door to new antitumor interventions.
authors.affiliation: Cardiovascular Research Center, CSIC-ICCC, IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, Sant Antoni Mª Claret, 167 08025, Barcelona, Spain. david.degonzalo@gmail.com.
authors.forename: David
authors.initials: D
authors.lastname: de Gonzalo-Calvo
authors.affiliation: Department of Pathology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. llopezv@santpau.cat.|Institut d'Investigacions Biomèdiques Sant Pau (IIB-Sant Pau), Barcelona, Spain. llopezv@santpau.cat.
authors.forename: Laura
authors.initials: L
authors.lastname: López-Vilaró
authors.affiliation: Cardiovascular Research Center, CSIC-ICCC, IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, Sant Antoni Mª Claret, 167 08025, Barcelona, Spain. lnasarre@csic-iccc.org.
authors.forename: Laura
authors.initials: L
authors.lastname: Nasarre
authors.affiliation: Institut d'Investigacions Biomèdiques Sant Pau (IIB-Sant Pau), Barcelona, Spain. mperez@santpau.cat.
authors.forename: Maitane
authors.initials: M
authors.lastname: Perez-Olabarria
authors.affiliation: Institut d'Investigacions Biomèdiques Sant Pau (IIB-Sant Pau), Barcelona, Spain. tvazquez@santpau.cat.
authors.forename: Tania
authors.initials: T
authors.lastname: Vázquez
authors.affiliation: Institut d'Investigacions Biomèdiques Sant Pau (IIB-Sant Pau), Barcelona, Spain. descuin@santpau.cat.
authors.forename: Daniel
authors.initials: D
authors.lastname: Escuin
authors.affiliation: Cardiovascular Research Center, CSIC-ICCC, IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, Sant Antoni Mª Claret, 167 08025, Barcelona, Spain. lbadimon@csic-iccc.org.
authors.forename: Lina
authors.initials: L
authors.lastname: Badimon
authors.affiliation: Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. abarnadas@santpau.cat.|Universitat Autònoma de Barcelona (UAB), Bellaterra (Cerdanyola del Vallès), Barcelona, Spain. abarnadas@santpau.cat.
authors.forename: Agusti
authors.initials: A
authors.lastname: Barnadas
authors.affiliation: Department of Pathology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. elerma@santpau.cat.|Universitat Autònoma de Barcelona (UAB), Bellaterra (Cerdanyola del Vallès), Barcelona, Spain. elerma@santpau.cat.
authors.forename: Enrique
authors.initials: E
authors.lastname: Lerma
authors.affiliation: Cardiovascular Research Center, CSIC-ICCC, IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, Sant Antoni Mª Claret, 167 08025, Barcelona, Spain. cllorente@csic-iccc.org.
authors.forename: Vicenta
authors.initials: V
authors.lastname: Llorente-Cortés
mesh_terms: D000101:Acetyl-CoA C-Acetyltransferase / Q000096:biosynthesis; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics; D002788:Cholesterol Esters / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009367:Neoplasm Staging; D011973:Receptors, LDL / Q000096:biosynthesis; D051122:Scavenger Receptors, Class B / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; D002788:Cholesterol Esters; C573412:LDLR protein, human; D011973:Receptors, LDL; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; C506639:ACAT1 protein, human; D000101:Acetyl-CoA C-Acetyltransferase