The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Detecting Activation of Ribosomal Protein S6 Kinase by Complementary DNA and Tissue Microarray Analysis
Abstract
BACKGROUND: Studies by comparative genomic hybridization (CGH) have shown that chromosomal region 17q23 is amplified in up to 20% of primary breast cancers. We used microarray analyses to measure the expression levels of genes in this region and to explore their prognostic importance. METHODS: A microarray that contained 4209 complementary DNA (cDNA) clones was used to identify genes that are overexpressed in the MCF-7 breast cancer cell line as compared with normal mammary tissue. Fluorescence in situ hybridization was used to analyze the copy number of one overexpressed gene, ribosomal protein S6 kinase (S6K), and to localize it to the 17q23 region. Northern and western blot analyses were used to measure S6K gene and protein expression, and an enzymatic assay was used to measure S6K activity. Tumor tissue microarray analysis was used to study amplification of S6K and the HER-2 oncogene, another 17q-linked gene, and the relationship between amplification and prognosis was analyzed. The Kaplan-Meier method was used for data analysis, and the log-rank test was used for statistical analysis. All P values are two-sided. RESULTS: S6K was amplified and highly overexpressed in MCF-7 cells relative to normal mammary epithelium, and protein expression and enzyme activity were increased. S6K was amplified in 59 (8.8%) of 668 primary breast tumors, and a statistically significant association between amplification and poor prognosis (P =.0021) was observed. Amplification of both S6K and HER-2 implied particularly poor survival (P =.0001). CONCLUSIONS: The combination of CGH information with cDNA and tissue microarray analyses can be used to identify amplified and overexpressed genes and to evaluate the clinical implications of such genes and genomic rearrangements. S6K is likely to be one of the genes at 17q23 that is amplified during oncogenesis and may adversely affect the prognosis of patients with this amplification.
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Cites
Phosphorylation and Activation of p70 s6k by PDK1
Pullen, N., Dennis, P. B., Andjelkovic, M., Dufner, A., Kozma, S. C., Hemmings, B. A., & Thomas, G. (1998) · Science · doi:10.1126/science.279.5351.707 · Cited by 826
TOR signalling and control of cell growth
Thomas, G., & Hall, M. N. (1997) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(97)80078-6 · Cited by 462 · cited 2×
“The S6K protein is rapidly activated in response to various mitogenic stimuli, such as growth factors (e.g., epidermal growth factor and platelet-derived growth factor), cytokines, and oncogene products (28,31, 32 ).”
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Cited by
TOR signaling in growth and metabolism
Wullschleger, S., Loewith, R., & Hall, M. N. (2006) · Cell · doi:10.1016/j.cell.2006.01.016 · Cited by 5,787
The mTOR Signalling Pathway in Human Cancer
Pópulo, H., Lopes, J. M., & Soares, P. (2012) · International Journal of Molecular Sciences · doi:10.3390/ijms13021886 · Cited by 830
Chromosome aberrations in solid tumors
Albertson, D. G., Collins, C., McCormick, F., & Gray, J. W. (2003) · Nature Genetics · doi:10.1038/ng1215 · Cited by 812
Targeting the mTOR Signaling Network for Cancer Therapy
Meric-Bernstam, F., & Gonzalez-Angulo, A. M. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.20.0766 · Cited by 639
Steelman, L. S., Chappell, W. H., Abrams, S. L., Kempf, C. R., Long, J., Laidler, P., Mijatovic, S., Maksimovic-Ivanic, D., Stivala, F., Mazzarino, M. C., et al. (2011) · Aging · doi:10.18632/aging.100296 · Cited by 553
Metadata
- Authors
- Barlund, M., Forozan, F., Kononen, J., Bubendorf, L., Chen, Y., Bittner, M. L., Torhorst, J., Haas, P., Bucher, C., Sauter, G., Kallioniemi, O.-P., & Kallioniemi, A.
- Venue
- JNCI Journal of the National Cancer Institute
- Publisher
- Oxford University Press (OUP)
- Published
- 2000-08-02
- Volume
- 92
- Issue
- 15
- Pages
- 1252-1259
- ISSN
- 0027-8874 (ISSN-L)
- 1460-2105
- OpenAlex
- W2130811967
- Cited by
- 275
- References
- 2
- FWCI
- 9.55
- Type
- journal article
- Language
- en
- Open access
- closed
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- Barlund, M., Forozan, F., Kononen, J., Bubendorf, L., Chen, Y., Bittner, M. L., Torhorst, J., Haas, P., Bucher, C., Sauter, G., Kallioniemi, O.-P., & Kallioniemi, A. (2000). Detecting Activation of Ribosomal Protein S6 Kinase by Complementary DNA and Tissue Microarray Analysis. JNCI Journal of the National Cancer Institute. https://doi.org/10.1093/jnci/92.15.1252
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