title: 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.
abstract: 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.
authors.affiliation: Institut de Biologie Moléculaire, UMR 9942, CNRS 1919, Montpellier, France.
authors.forename: F
authors.initials: F
authors.lastname: Courjal
authors.forename: G
authors.initials: G
authors.lastname: Louason
authors.forename: P
authors.initials: P
authors.lastname: Speiser
authors.forename: D
authors.initials: D
authors.lastname: Katsaros
authors.forename: R
authors.initials: R
authors.lastname: Zeillinger
authors.forename: C
authors.initials: C
authors.lastname: Theillet
mesh_terms: D015152:Blotting, Northern; D015139:Blotting, Southern; D001943:Breast Neoplasms / Q000235:genetics*; D019938:Cyclin D1; D016213:Cyclins / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005784:Gene Amplification; D015870:Gene Expression; D006801:Humans; D015513:Oncogene Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000032:analysis; D014407:Tumor Cells, Cultured
chemical_list: D016213:Cyclins; D004273:DNA, Neoplasm; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D019938:Cyclin D1; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt