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| Gene expression signatures identify novel regulatory pathways during murine lung development: implications for lung tumorigenesis |
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| Author(s): Bonner AE, Lemon WJ, You M |
| Source: JOURNAL OF MEDICAL GENETICS Volume: 40 Issue: 6 Pages: 408-417 Published: JUN 2003 |
| Times Cited: 35 References: 23 |
| Abstract: Oligonucleotide array based analysis was conducted to examine the temporal pattern of gene expression across the various stages of lung development to identify regulatory pathways at key developmental time points. Whole embryo total RNA or embryonic lung total RNA was harvested from A/J mice at seven developmental stages. To investigate changes in gene expression during lung development, four samples from each stage were examined using Affymetrix U74Av2 murine oligonucleotide microarrays. From the over 12 000 genes and ESTs represented on the array, 1346 genes and ESTs were identified as having a significant change in expression between at least one time point and the others (p < 0.001, Kruskal-Wallis test). Within this group of &SIM;1300 genes, four patterns of expression were seen: (1) upregulation during the embryonic period of development (up-down); (2) upregulation during the postnatal period of lung development (down-up) and (3) fluctuating expression, up initially, down for one or more time points, and then up again (up-down-up); and (4) vice versa (down-up-down). Expression patterns of genes previously reported to be involved in pulmonary development were also examined. Using the pathway visualisation tool, GenMapp, at least three regulatory pathways were found to contain clusters of differentially expressed genes: Wnt signalling, cell cycle, and apoptosis. Furthermore, we have shown that many of the genes involved in lung development are either known oncogenes or tumour suppressor genes altered in lung cancer, such as Cyr61, Rassf1a, and Dutt1/Robo1, or putative lung cancer genes. In addition, the genes identified pertinent to early development may also serve as candidate susceptibility genes for various inherited lung cancer disorders as well as for various heritable disorders of lung development. These results will contribute to our understanding of novel aspects of the regulatory machinery for embryonic lung development and of the genes involved in lung tumorigenesis. |
| Document Type: Article |
| Language: English |
| Reprint Address: You, M (reprint author), Washington Univ, Sch Med, Dept Surg, Campus Box 8109,660 S Euclid Ave, St Louis, MO 63110 USA |
Addresses:
1. Ohio State Univ, Ctr Comprehens Canc, Div Human Canc Genet, Columbus, OH 43210 USA |
| Publisher: BRITISH MED JOURNAL PUBL GROUP, BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND |
| Subject Category: Genetics & Heredity |
| IDS Number: 689RD |
| ISSN: 0022-2593 |
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