title: Amplification of chromosome 8q21-qter associated with the acquired paclitaxel resistance of nasopharyngeal carcinoma cells.
abstract: OBJECTIVE
  to observe relationship between chromosome imbalance and taxol resistance in nasopharyngeal carcinoma (NPC).
  
  
  METHODS
  three taxol-resistant sub-lines were established through repeated exposure of escalating doses of paclitaxel to NPC cell lines (CNE-1, HNE-2 and 5-8F). The change of copy number of chromosomes was investigated by the genome-wide analyses of comparative genomic hybridization (CGH). Gene profiles of both parental and resistant cell lines were determined by cDNA microarray. Cell viability was assayed by colony formation assay.
  
  
  RESULTS
  The taxol resistant sub-lines (CNE1/Taxol, HNE2/Taxol and 5-8F/Taxol) developed displayed an average 5~8-fold higher IC50 value than their parental cells. The common losses of chromosome 18, 10q11-qter and gains of chromosome 12, 3q21-qter, 5p13-pter and 20q11-qter were observed by CGH in all of 6 NPC cell lines. A common gain region of chromosome 8q21-qter was identified in taxol resistant sub-lines. 15 genes of 762 transcripts on this chromosome region were consistently up-regulated detected by cDNA microarray in three taxol resistant sub-lines, and functionally clustered into various groups, including genes related to vascular formation vascular formation (ANGPT1), apoptosis (MYC, TOP1MT), cell adhesion and cell cycle (PPP1R16A, SDC2, CA2, ANKRD46), gene regulation (HRSP12, ZNF696, SLC39A4, POP1), metabolism (PYCRL). Inhibition of ANGPT1 expression significantly increased the sensitivity of CNE-1/taxol to paclitaxol.
  
  
  CONCLUSIONS
  The common gain of chromosome 8q21-qter in taxol resistant sublines predicates that potential candidate genes on this region may contribute to taxol resistant phenotype. ANGPT1 may be associated with taxol resistance of NPC cells.
authors.affiliation: Department of Otoalryngology-Head Neck Surgery, Third Xiangya Hospital, Central South University Changsha 410013, Hunan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Otoalryngology-Head Neck Surgery, Third Xiangya Hospital, Central South University Changsha 410013, Hunan, China.
authors.forename: Yating
authors.initials: Y
authors.lastname: You
authors.affiliation: Department of Otoalryngology-Head Neck Surgery, Third Xiangya Hospital, Central South University Changsha 410013, Hunan, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Otoalryngology-Head Neck Surgery, Third Xiangya Hospital, Central South University Changsha 410013, Hunan, China.
authors.forename: Yexun
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Central laboratory, Third Xiangya Hospital, Central South University Changsha 410013, Hunan, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xiang
authors.affiliation: Department of Head and Neck Surgery, The Affiliated Cancer Hospital of Xiangya Medical School, Central South University Changsha 410013, Hunan, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Head and Neck Surgery, Peace Hospital of Changzhi Medical College Changzhi 046000, Shangxi, China.
authors.forename: Jiangbo
authors.initials: J
authors.lastname: Qin
authors.affiliation: Department of Otoalryngology-Head Neck Surgery, Third Xiangya Hospital, Central South University Changsha 410013, Hunan, China.
authors.forename: Guolin
authors.initials: G
authors.lastname: Tan
mesh_terms: D042683:Angiopoietin-1 / Q000235:genetics*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D015153:Blotting, Western; D002277:Carcinoma; D045744:Cell Line, Tumor; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005784:Gene Amplification; D020869:Gene Expression Profiling; D006801:Humans; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D017239:Paclitaxel / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome
chemical_list: C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel
keywords: Angiopoietin; chromosome imbalance; drug resistance; nasopharyngeal carcinoma