title: Calcitriol supplementation effects on Ki67 expression and transcriptional profile of breast cancer specimens from post-menopausal patients.
abstract: OBJECTIVE
  High concentration of 1,25(OH)2D3 (50-100 nM), which cause hypercalcemia in vivo, induce the hormone transcriptional targets and exert antiproliferative effects in cultured breast cancer lineages, however, no studies investigated whether these effects might be reproduced in tumor specimens in vivo. Our aim was to evaluate the effects of calcitriol supplementation on the proliferative index (Ki67 expression) and gene expression profile of post-menopausal breast cancer samples.
  
  
  RESULTS
  Tumor samples were collected from 33 patients, most of whom (87.5%) presenting 25(OH)D3 insufficiency, before and after a short term calcitriol supplementation (0.50 μg/day PO, for 30 days). Tumor dimension remained stable in ultrasound evaluations. A slight reduction in Ki67 immunoexpression was detected, however in only 10/32 post-calcitriol samples an expressively low proliferative index [Ln (%Ki67+) < 1] was achieved. Gene expression from 15 matched pre/post-supplementation samples was analyzed by microarray (U133 Plus 2.0 GeneChip, Affymetrix) and 15 genes were over-expressed in post-supplementation tumors, including FOS and EGR1, which were previously shown to be regulated by vitamin D. However, these results were not confirmed in another four breast cancer samples.
  
  
  CONCLUSIONS
  Calcitriol supplementation is neither sufficient to expressively elicit an antiproliferative response nor to induce the hormone transcriptional signaling pathway in breast cancer specimens.
authors.affiliation: Departamento de Radiologia e Oncologia, LIM24, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Yuri Nagamine
authors.initials: YN
authors.lastname: Urata
authors.affiliation: Departamento de Radiologia e Oncologia, LIM24, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil; Instituto Brasileiro de Controle do Câncer, São Paulo, SP, Brazil.
authors.forename: Eduardo Carneiro de
authors.initials: EC
authors.lastname: Lyra
authors.affiliation: Departamento de Radiologia e Oncologia, LIM24, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Maria Lucia Hirata
authors.initials: ML
authors.lastname: Katayama
authors.affiliation: Instituto Brasileiro de Controle do Câncer, São Paulo, SP, Brazil.
authors.forename: Ricardo Alves
authors.initials: RA
authors.lastname: Basso
authors.affiliation: Instituto Brasileiro de Controle do Câncer, São Paulo, SP, Brazil.
authors.forename: Paulo Eduardo Zuccolotto de
authors.initials: PE
authors.lastname: Assis
authors.affiliation: Consultoria em Patologia, São Paulo, SP, Brazil.
authors.forename: Ana Paula Torres
authors.initials: AP
authors.lastname: Cardoso
authors.affiliation: Departamento de Radiologia e Oncologia, LIM24, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Rosimeire Aparecida
authors.initials: RA
authors.lastname: Roela
authors.affiliation: Departamento de Patologia, Instituto Adolfo Lutz, São Paulo, SP, Brazil.
authors.forename: Suely
authors.initials: S
authors.lastname: Nonogaki
authors.affiliation: Instituto Brasileiro de Controle do Câncer, São Paulo, SP, Brazil.
authors.forename: João Carlos Guedes
authors.initials: JC
authors.lastname: Sampaio Góes
authors.affiliation: Departamento de Radiologia e Oncologia, LIM24, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: M Mitzi
authors.initials: MM
authors.lastname: Brentani
authors.affiliation: Departamento de Radiologia e Oncologia, LIM24, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil. Electronic address: makoike@lim24.fm.usp.br.
authors.forename: Maria Aparecida Azevedo Koike
authors.initials: MA
authors.lastname: Folgueira
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002117:Calcitriol / Q000008:administration & dosage*; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects; D019587:Dietary Supplements; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D016761:Oncogene Proteins v-fos / Q000235:genetics / Q000378:metabolism; D017698:Postmenopause; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D019394:Ki-67 Antigen; D016761:Oncogene Proteins v-fos; D002117:Calcitriol
keywords: Breast cancer; Calcitriol; Gene expression; Proliferative index