Unknown,Transcriptomics,Genomics,Proteomics

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The addition of chromosome 8 leads to characteristic dysregulation of gene expression on all chromosome and transformed-associated phenotypes

ABSTRACT: To examain effects of trisomy 8 on gene expression in normal human cells, we have employed whole genome microarray expression profiling. To study the effects of aneuploidy in normal human cells, we generated cells which are artificially trisomic chromosome 8 (trisomy 8) using human primary fibroblast cells by microcell-mediated chromosome transfer (HE35tri8 clones). Gene expression in trisomy 8 clones (HE35tri8-1, 2 and3) and euploid clones (HE35-1, 2 and 4). Three independent experiments were performed at each clone.

ORGANISM(S): Homo sapiens

SUBMITTER: Hisakatsu Nawata

PROVIDER: E-GEOD-28076 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Dysregulation of gene expression in the artificial human trisomy cells of chromosome 8 associated with transformed cell phenotypes.

Nawata Hisakatsu H Kashino Genro G Tano Keizo K Daino Kazuhiro K Shimada Yoshiya Y Kugoh Hiroyuki H Oshimura Mitsuo M Watanabe Masami M

PloS one 20110929 9

A change in chromosome number, known as aneuploidy, is a common characteristic of cancer. Aneuploidy disrupts gene expression in human cancer cells and immortalized human epithelial cells, but not in normal human cells. However, the relationship between aneuploidy and cancer remains unclear. To study the effects of aneuploidy in normal human cells, we generated artificial cells of human primary fibroblast having three chromosome 8 (trisomy 8 cells) by using microcell-mediated chromosome transfer ...[more]

PMID: 21980425

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Project description:An increased serum alkaline phosphatase concentration is known to be associated with a negative prognosis in canine and human osteosarcoma. To expand upon previous studies regarding the biological relevance of increased serum alkaline phosphatase as a negative prognostic factor, xenogeneic heterotopic transplants were performed using six canine primary osteosarcoma cell lines generated from patients with differing serum alkaline phosphatase concentrations (3 normal and 3 increased). Three of the six cell lines were capable of generating tumors and tumor formation was independent of the serum alkaline phosphatase status of the cell line. Microarray analysis identified 379 genes as being differentially-expressed between the tumorigenic and non-tumorigenic cell lines. Frizzled-6 was up-regulated to the greatest extent (7.78 fold) in tumorigenic cell lines compared to non-tumorigenic cell lines. Frizzled-6, a co-receptor for Wnt ligands has been associated with enhanced tumor-initiating cells and poor prognosis for other tumors. The increased expression of frizzled-6 was confirmed by QPCR and Western blot analysis. Additionally, the tumorigenic cell lines also had an increase in the percentage of side population cells compared to non-tumorigenic cell lines (5.89% versus 1.58%, respectively). There were no differences in tumorigenicity, frizzled-6, or percentage of side population cells noted between osteosarcoma cell lines generated from patients of differing serum alkaline phosphatase concentration. However, to our knowledge this is the first study to identified frizzled-6 as a possible marker of osteosarcoma cell populations with enhanced tumorigenicity and side population cells. Future work will focus on defining the role of frizzled-6 in osteosarcoma tumorigenesis and tumor-initiating cells. A total of six canine primary osteosarcoma cell lines were used in this study. Three cell lines were capable of forming tumors when transplanted into mice (tumorigenic) and three cell lines were not capable of forming tumors upon transplant into mice (non-tumorigenic). The gene expression data is from the primary cell lines, not the transplanted cells. There were no reference cell lines or controls used in this study.

Dataset Information

The addition of chromosome 8 leads to characteristic dysregulation of gene expression on all chromosome and transformed-associated phenotypes

Publications

Dysregulation of gene expression in the artificial human trisomy cells of chromosome 8 associated with transformed cell phenotypes.

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