title: Expression of anti-apoptosis genes determines the response of adrenal cancer to apoptosis-inducing chemotherapy.
abstract: BACKGROUND
  This study tested the hypothesis that response of adrenal cortical carcinoma (ACC) to pro-apoptosis drugs depends on expression of anti-apoptosis genes.
  
  
  METHODS
  Expression of Bcl-2 and Bcl-XL proteins was determined in two human adrenal cancer cell lines, NCI-H-295 and RL-251. Two pro-apoptosis drugs, gossypol (G) and docetaxel (D) were tested in vitro and in vivo in a human ACC/SCID mouse chimera.
  
  
  RESULTS
  Bcl-XL was strongly expressed in RL-251 but not in H-295 and neither expressed the Bcl-2 protein. G and D induced greater dose-dependent inhibition of cell proliferation in RL-251 than in H-295 cells and completely suppressed growth of tumors with high expression of Bcl-XL (p<0.05) while there was no growth suppression in tumors without Bcl-XL expression.
  
  
  CONCLUSIONS
  This study provided proof of concept that expression of Bcl-XL determines response to pro-apoptosis drugs. Profiling adrenal tumors for expression of anti-apoptosis genes may provide clues to their potential response to drugs that induce apoptosis.
authors.affiliation: Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Rm 5570, MSRB 2, 1150 West Medical Center Dr, Ann Arbor MI 48109, USA. dschtein@umich.edu
authors.forename: David E
authors.initials: DE
authors.lastname: Schteingart
authors.forename: Ricardo
authors.initials: R
authors.lastname: Benitez
authors.forename: Carol
authors.initials: C
authors.lastname: Bradford
authors.forename: Ajita
authors.initials: A
authors.lastname: Narayan
authors.forename: Shaomeng
authors.initials: S
authors.lastname: Wang
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D045744:Cell Line, Tumor; D000077143:Docetaxel; D019254:Genes, bcl-2; D006072:Gossypol / Q000494:pharmacology; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D043823:Taxoids / Q000494:pharmacology; D051020:bcl-X Protein / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C494811:BCL2L1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D043823:Taxoids; D051020:bcl-X Protein; D000077143:Docetaxel; D006072:Gossypol