© 2000 by Oxford University Press
Journal of the National Cancer Institute, Vol. 92, No. 15, 1252-1259,
August 2, 2000
© 2000 Oxford University Press
REPORTS |
Detecting Activation of Ribosomal Protein S6 Kinase by Complementary DNA and Tissue Microarray Analysis
Affiliations of authors: M. Bärlund, Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, and Laboratory of Cancer Genetics, Institute of Medical Technology, University of Tampere and Tampere University Hospital, Finland; F. Forozan, J. Kononen, L. Bubendorf, Y. Chen, M. L. Bittner, O.-P. Kallioniemi, A. Kallioniemi, Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health; J. Torhorst, P. Haas, C. Bucher, G. Sauter, Institute of Pathology, University of Basel, Switzerland.
Correspondence to: Anne Kallioniemi, M.D., National Institutes of Health, 49 Convent Dr., Rm. 4B24, Bethesda, MD 20892-4470 (e-mail: akallion{at}nhgri.nih.gov).
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.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A Lugli, I Zlobec, K Baker, P Minoo, L Tornillo, L Terracciano, and J R Jass Prognostic significance of mucins in colorectal cancer with different DNA mismatch-repair status J. Clin. Pathol., May 1, 2007; 60(5): 534 - 539. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Kuuselo, K. Savinainen, D. O. Azorsa, G. D. Basu, R. Karhu, S. Tuzmen, S. Mousses, and A. Kallioniemi Intersex-like (IXL) Is a Cell Survival Regulator in Pancreatic Cancer with 19q13 Amplification Cancer Res., March 1, 2007; 67(5): 1943 - 1949. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. TIAN, A. CHAKRABARTI, N. V. AMIRKHANOV, M. R. ARUVA, K. ZHANG, B. MATHEW, C. CARDI, W. QIN, E. R. SAUTER, M. L. THAKUR, et al. External Imaging of CCND1, MYC, and KRAS Oncogene mRNAs with Tumor-Targeted Radionuclide-PNA-Peptide Chimeras Ann. N.Y. Acad. Sci., November 1, 2005; 1059(1): 106 - 144. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Nessling, K. Richter, C. Schwaenen, P. Roerig, G. Wrobel, S. Wessendorf, B. Fritz, M. Bentz, H.-P. Sinn, B. Radlwimmer, et al. Candidate Genes in Breast Cancer Revealed by Microarray-Based Comparative Genomic Hybridization of Archived Tissue Cancer Res., January 15, 2005; 65(2): 439 - 447. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Al-Kuraya, P. Schraml, J. Torhorst, C. Tapia, B. Zaharieva, H. Novotny, H. Spichtin, R. Maurer, M. Mirlacher, O. Kochli, et al. Prognostic Relevance of Gene Amplifications and Coamplifications in Breast Cancer Cancer Res., December 1, 2004; 64(23): 8534 - 8540. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Koziczak and N. E. Hynes Cooperation between Fibroblast Growth Factor Receptor-4 and ErbB2 in Regulation of Cyclin D1 Translation J. Biol. Chem., November 26, 2004; 279(48): 50004 - 50011. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Fernandez-Madrid, N. Tang, H. Alansari, J. L. Granda, L. Tait, K. C. Amirikia, M. Moroianu, X. Wang, and R. L. Karvonen Autoantibodies to Annexin XI-A and Other Autoantigens in the Diagnosis of Breast Cancer Cancer Res., August 1, 2004; 64(15): 5089 - 5096. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Woelfle, G. Sauter, S. Santjer, R. Brakenhoff, and K. Pantel Down-Regulated Expression of Cytokeratin 18 Promotes Progression of Human Breast Cancer Clin. Cancer Res., April 15, 2004; 10(8): 2670 - 2674. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-C. Noh, W. H. Mondesire, J. Peng, W. Jian, H. Zhang, J. Dong, G. B. Mills, M.-C. Hung, and F. Meric-Bernstam Determinants of Rapamycin Sensitivity in Breast Cancer Cells Clin. Cancer Res., February 1, 2004; 10(3): 1013 - 1023. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Simon, S. Panussis, R. Maurer, H. Spichtin, K. Glatz, C. Tapia, M. Mirlacher, A. Rufle, J. Torhorst, and G. Sauter KIT (CD117)-Positive Breast Cancers Are Infrequent and Lack KIT Gene Mutations Clin. Cancer Res., January 1, 2004; 10(1): 178 - 183. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Vrolijk, W. Sloos, W. Mesker, P. Franken, R. Fodde, H. Morreau, and H. Tanke Automated Acquisition of Stained Tissue Microarrays for High-Throughput Evaluation of Molecular Targets J. Mol. Diagn., August 1, 2003; 5(3): 160 - 167. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Hirasawa, F. Saito-Ohara, J. Inoue, D. Aoki, N. Susumu, T. Yokoyama, S. Nozawa, J. Inazawa, and I. Imoto Association of 17q21-q24 Gain in Ovarian Clear Cell Adenocarcinomas with Poor Prognosis and Identification of PPM1D and APPBP2 as Likely Amplification Targets Clin. Cancer Res., June 1, 2003; 9(6): 1995 - 2004. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. J. Shah, S. Ghosh, and T. Hunter Mitotic Regulation of Ribosomal S6 Kinase 1 Involves Ser/Thr, Pro Phosphorylation of Consensus and Non-consensus Sites by Cdc2 J. Biol. Chem., April 25, 2003; 278(18): 16433 - 16442. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Hyman, P. Kauraniemi, S. Hautaniemi, M. Wolf, S. Mousses, E. Rozenblum, M. Ringner, G. Sauter, O. Monni, A. Elkahloun, et al. Impact of DNA Amplification on Gene Expression Patterns in Breast Cancer Cancer Res., November 1, 2002; 62(21): 6240 - 6245. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. K. Hoyer, S. W. French, D. E. Turner, M. T. N. Nguyen, M. Renard, C. S. Malone, S. Knoetig, C.-F. Qi, T. T. Su, H. Cheroutre, et al. Dysregulated TCL1 promotes multiple classes of mature B cell lymphoma PNAS, October 29, 2002; 99(22): 14392 - 14397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. L. Kenerson, L. D. Aicher, L. D. True, and R. S. Yeung Activated Mammalian Target of Rapamycin Pathway in the Pathogenesis of Tuberous Sclerosis Complex Renal Tumors Cancer Res., October 15, 2002; 62(20): 5645 - 5650. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Meric and K. K. Hunt Translation Initiation in Cancer: A Novel Target for Therapy Mol. Cancer Ther., September 1, 2002; 1(11): 971 - 979. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. F. Macgregor and J. A. Squire Application of Microarrays to the Analysis of Gene Expression in Cancer Clin. Chem., August 1, 2002; 48(8): 1170 - 1177. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Sinclair, C. Adem, A. Naderi, C. L. Soderberg, M. Johnson, L. Wadum, V. L. Couch, T. A. Sellers, D. Schaid, J. Slezak, et al. TBX2 Is Preferentially Amplified in BRCA1- and BRCA2-related Breast Tumors Cancer Res., July 1, 2002; 62(13): 3587 - 3591. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Andersen, O. Monni, U. Wagner, J. Kononen, M. Barlund, C. Bucher, P. Haas, A. Nocito, H. Bissig, G. Sauter, et al. High-Throughput Copy Number Analysis of 17q23 in 3520 Tissue Specimens by Fluorescence in Situ Hybridization to Tissue Microarrays Am. J. Pathol., July 1, 2002; 161(1): 73 - 79. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Mousses, L. Bubendorf, U. Wagner, G. Hostetter, J. Kononen, R. Cornelison, N. Goldberger, A. G. Elkahloun, N. Willi, P. Koivisto, et al. Clinical Validation of Candidate Genes Associated with Prostate Cancer Progression in the CWR22 Model System using Tissue Microarrays Cancer Res., March 1, 2002; 62(5): 1256 - 1260. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Belbin, B. Singh, I. Barber, N. Socci, B. Wenig, R. Smith, M. B. Prystowsky, and G. Childs Molecular Classification of Head and Neck Squamous Cell Carcinoma Using cDNA Microarrays Cancer Res., February 1, 2002; 62(4): 1184 - 1190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Schoenberg Fejzo and D. J. Slamon Frozen Tumor Tissue Microarray Technology for Analysis of Tumor RNA, DNA, and Proteins Am. J. Pathol., November 1, 2001; 159(5): 1645 - 1650. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Caristi, J. L. Galera, F. Matarese, M. Imai, S. Caporali, M. Cancemi, L. Altucci, L. Cicatiello, D. Teti, F. Bresciani, et al. Estrogens Do Not Modify MAP Kinase-dependent Nuclear Signaling during Stimulation of Early G1 Progression in Human Breast Cancer Cells Cancer Res., September 1, 2001; 61(17): 6360 - 6366. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Podsypanina, R. T. Lee, C. Politis, I. Hennessy, A. Crane, J. Puc, M. Neshat, H. Wang, L. Yang, J. Gibbons, et al. An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten+/- mice PNAS, August 10, 2001; (2001) 171060098. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Simon, J. Richter, U. Wagner, A. Fijan, J. Bruderer, U. Schmid, D. Ackermann, R. Maurer, G. Alund, H. Knonagel, et al. High-Throughput Tissue Microarray Analysis of 3p25 (RAF1) and 8p12 (FGFR1) Copy Number Alterations in Urinary Bladder Cancer Cancer Res., June 1, 2001; 61(11): 4514 - 4519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Monni, M. Bärlund, S. Mousses, J. Kononen, G. Sauter, M. Heiskanen, P. Paavola, K. Avela, Y. Chen, M. L. Bittner, et al. Comprehensive copy number and gene expression profiling of the 17q23 amplicon in human breast cancer PNAS, April 25, 2001; (2001) 91582298. [Abstract] [Full Text]
|
|
|
|
 |
|
 O.-P. Kallioniemi, U. Wagner, J. Kononen, and G. Sauter Tissue microarray technology for high-throughput molecular profiling of cancer Hum. Mol. Genet., April 1, 2001; 10(7): 657 - 662. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Bärlund, O. Monni, J. Kononen, R. Cornelison, J. Torhorst, G. Sauter, O.-P. Kallioniemi, and A. Kallioniemi Multiple Genes at 17q23 Undergo Amplification and Overexpression in Breast Cancer Cancer Res., October 1, 2000; 60(19): 5340 - 5344. [Abstract] [Full Text]
|
|
|
|
|
|
O. Monni, M. Barlund, S. Mousses, J. Kononen, G. Sauter, M. Heiskanen, P. Paavola, K. Avela, Y. Chen, M. L. Bittner, et al. Comprehensive copy number and gene expression profiling of the 17q23 amplicon in human breast cancer PNAS, May 8, 2001; 98(10): 5711 - 5716. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Podsypanina, R. T. Lee, C. Politis, I. Hennessy, A. Crane, J. Puc, M. Neshat, H. Wang, L. Yang, J. Gibbons, et al. An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten+/- mice PNAS, August 28, 2001; 98(18): 10320 - 10325. [Abstract] [Full Text] [PDF]
|
|