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

Courjal, F.; Louason, G.; Speiser, P.; Katsaros, D.; Zeillinger, R.; Theillet, C.

Int J Cancer

1996-08-22 / vol 69 / pages 247-53


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.

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Female; Humans; Blotting, Southern; *Gene Expression; Blotting, Northern; RNA, Messenger/metabolism; Tumor Cells, Cultured; Proto-Oncogene Proteins c-akt; Protein-Serine-Threonine Kinases/genetics; Breast Neoplasms/*genetics; *Proto-Oncogene Proteins; *Gene Amplification; Cyclin D1; Cyclins/*genetics; DNA, Neoplasm/analysis; Oncogene Proteins/*genetics; Ovarian Neoplasms/*genetics; Receptors, Estrogen/analysis

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