Cyclin gene amplification and overexpression in breast and ovarian cancers: Evidence for the selection of cyclin D1 in breast and cyclin E in ovarian tumors

• Published in: International journal of cancer Vol. 69; no. 4; pp. 247 - 253
• Main Authors: Courjal, Frank, Louason, Geneviève, Speiser, Paul, Katsaros, Dionisios, Zeillinger, Robert, Theillet, Charles
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 22.08.1996; Wiley
• Subjects: Biochemistry, Molecular Biology; Blotting, Northern; Blotting, Southern; Breast Neoplasms - genetics; Cyclin D1; Cyclins - genetics; DNA, Neoplasm - analysis; Female; Gene Amplification; Gene Expression; Humans; Life Sciences; Oncogene Proteins - genetics; Ovarian Neoplasms - genetics; Protein-Serine-Threonine Kinases - genetics; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Receptors, Estrogen - analysis; RNA, Messenger - metabolism; Tumor Cells, Cultured; Neoplasm/analysis Female Gene Amplification Gene Expression Humans Oncogene Proteins/genetics Ovarian Neoplasms/genetics Protein-Serine-Threonine Kinases/genetics Proto-Oncogene Proteins Proto-Oncogene Proteins c-akt RNA; Southern Breast Neoplasms/genetics Cyclin D1 Cyclins/genetics DNA; Messenger/metabolism Receptors; Cultured; Northern Blotting; Estrogen/analysis Tumor Cells; Blotting
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/(SICI)1097-0215(19960822)69:4<247::AID-IJC1>3.0.CO;2-X

Evidence of the involvement of cyclin genes in genetic alterations in human cancer is growing. In the present study, we investigated the amplification, in human breast and ovarian cancer, of 5 cyclin genes; cyclin A, cyclin D1, cyclin D2, cyclin D3 and cyclin E. For this purpose, a series of 1,171 breast and 237 ovarian tumors tested for DNA amplification by Southern blotting and a subset of 132 breast and 22 ovarian cancers were analyzed for RNA expression levels by slot‐blot and Northern blotting. In breast tumors, only cyclin D1 was found to be activated in a sizeable fraction of the tumors (amplification 12.6%, overexpression 19%). Cyclin A, D2, D3, and E genes never, or only on rare occasions, showed increased DNA copy numbers and were never found overexpressed at the RNA level. Amplification of cyclin D1 correlated with ER+ breast cancer and the presence of lymph‐node metastasis. Interestingly, we were also able to determine an association with invasive lobular carcinoma. Our data suggest that cyclin D1 activation determines the evolution of a particular subset of estrogen‐responsive tumors. Data obtained in ovarian tumors contrasted with observations in breast cancer. Cyclin D1 DNA amplification was much less frequent in ovarian than in breast tumors (3.3% vs. 12.6%), whereas cyclin E amplification and overexpression were observed in a significant number of cases (12.5% and 18.0% respectively). Cyclin A, cyclin D2 and D3 rarely showed anomalies at the DNA level and were never overexpressed. No clear correlation could be observed between amplification of the cyclin E gene and tumor type, stage or grade in ovarian cancer. Data presented here suggest distinct pathways of cyclin activation in human breast and ovarian cancer. © 1996 Wiley‐Liss, Inc.