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

Int J Cancer. 1996 Aug 22;69(4):247-53. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Cyclins
  • DNA, Neoplasm
  • Oncogene Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Receptors, Estrogen
  • Cyclin D1
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt