title: The role of the SHH gene in prostate cancer cell resistance to paclitaxel.
abstract: BACKGROUND
  The increased activity of the Sonic Hedgehog (SHH) pathway has been demonstrated in many types of cancer including prostate cancer (PCa). It has been shown that SHH pathway is involved in tumor angiogenesis and in regulation of metabolism of cancer stem cells. The increased activity of the SHH pathway is responsible for generation and maintenance of the multidrug resistance in cancer cells. A key role in the development of this insensitivity to cytotoxic drugs play ATP-binding cassette (ABC) transporters.
  
  
  METHODS
  SHH encoding plasmid was stably transfected into PCa cell lines DU145 and LNCaP. The expression of SHH was silenced by shRNA and the level of SHH was tested by quantitative (q)PCR and western blot methods. The effect of SHH overexpression in cells after treatment with paclitaxel was measured by MTT assay, crystal violet assay and flow cytometry. The level of 44 ABC transporters was estimated by qPCR.
  
  
  RESULTS
  Expression of exogenous SHH protein in DU145 and LNCaP cell lines enhanced their resistance to paclitaxel along with increased expression of ABC transporters transcripts. Paclitaxel treatment further enhanced the expression of increased ABC transporters transcripts in cells overexpressing SHH.
  
  
  CONCLUSIONS
  Overexpression of SHH enhances PCa cell lines resistance to paclitaxel. Higher level of SHH leads to increase in ABC transporters expression in a manner dependent on paclitaxel.
authors.affiliation: Department of Genetics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Statkiewicz
authors.forename: Natalia
authors.initials: N
authors.lastname: Maryan
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Lipiec
authors.forename: Emilia
authors.initials: E
authors.lastname: Grecka
authors.forename: Monika A
authors.initials: MA
authors.lastname: Grygorowicz
authors.forename: Marcin
authors.initials: M
authors.lastname: Omiotek
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Gorska
authors.forename: Michal
authors.initials: M
authors.lastname: Mikula
authors.forename: Maciej
authors.initials: M
authors.lastname: Malecki
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000502:physiology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D053823:Hedgehog Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D017239:Paclitaxel / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D014162:Transfection; D017211:Treatment Failure; D015854:Up-Regulation / Q000235:genetics / Q000502:physiology
chemical_list: D018528:ATP-Binding Cassette Transporters; D000972:Antineoplastic Agents, Phytogenic; D053823:Hedgehog Proteins; C509239:SHH protein, human; D017239:Paclitaxel
keywords: ATP-binding cassette transporters; multidrug resistance; paclitaxel; sonic Hedgehog