Expression profiling of the ovarian surface kinome reveals candidate genes for early neoplastic changes Journal Article
| Authors: | Pejovic, T.; Pande, N. T.; Mori, M.; Mhawech-Fauceglia, P.; Harrington, C.; Mongoue-Tchokote, S.; Dim, D.; Andrews, C.; Beck, A.; Tarumi, Y.; Djilas, J.; Cappuccini, F.; Caballero, O.; Huang, J.; Levy, S.; Tsiamouri, A.; Cain, J.; Bagby, G. C.; Strausberg, R. L.; Simpson, A. J.; Odunsi, K. O. |
| Article Title: | Expression profiling of the ovarian surface kinome reveals candidate genes for early neoplastic changes |
| Abstract: | OBJECTIVES: We tested the hypothesis that co-coordinated up-regulation or down-regulation of several ovarian cell surface kinases may provide clues for better understanding of the disease and help in rational design of therapeutic targets. STUDY DESIGN: We compared the expression signature of 69 surface kinases in normal ovarian surface epithelial cells (OSE), with OSE from patients at high risk and with ovarian cancer. RESULTS: Seven surface kinases, ALK, EPHA5, EPHB1, ERBB4, INSRR, PTK, and TGFβR1 displayed a distinctive linear trend in expression from normal, highrisk, and malignant epithelium. We confirmed these results using semiquantitative reverse transcription-polymerase chain reaction and tissue array of 202 ovarian cancer samples. A strong correlate was shown between disease-free survival and the expression of ERBB4.DNAsequencing revealed two novelmutations in ERBB4 in two cancer samples. CONCLUSIONS: A distinct subset of the ovarian surface kinome is altered in the transition from high risk to invasive cancer and genetic mutation is not a dominant mechanism for these modifications. These results have significant implications for early detection and targeted therapeutic approaches for women at high risk of developing ovarian cancer. Copyright © 2009 Neoplasia Press, Inc. All rights reserved. |
| Keywords: | adult; controlled study; human tissue; protein expression; aged; unclassified drug; gene mutation; cancer risk; disease free survival; cancer staging; reverse transcription polymerase chain reaction; ovary cancer; gene expression; high risk patient; correlation analysis; early diagnosis; quantitative analysis; membrane protein; epithelium cell; dna sequence; invasive carcinoma; tissue microarray; malignant transformation; alk; cell surface protein; ephrin receptor a5; ephrin receptor b1; epidermal growth factor receptor 4; insrr; ptk; transforming growth factor beta receptor 1 |
| Journal Title: | Translational Oncology |
| Volume: | 2 |
| Issue: | 4 |
| ISSN: | 1936-5233 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2009-12-01 |
| Start Page: | 341 |
| End Page: | 349 |
| Language: | English |
| DOI: | 10.1593/tlo.09199 |
| PROVIDER: | scopus |
| PMCID: | PMC2781076 |
| PUBMED: | 19956396 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 30 November 2010" - "Source: Scopus" |
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