title: Stable overexpression of cyclin D1 in a human mammary epithelial cell line prolongs the S-phase and inhibits growth.
abstract: Amplification and/or increased expression of cyclin D1 occurs in an appreciable fraction of primary human breast carcinomas and several other types of human cancer. In addition, overexpression of cyclin D1 in rodent fibroblasts enhances growth and malignant transformation. The present study demonstrates that the extent of amplification and expression of cyclin D1 varies widely amongst a series of cell lines established from normal human mammary epithelium or human breast carcinomas. The HBL-100 mammary epithelial cell line did not display amplification or increased expression of cyclin D1. We used retrovirus-mediated transduction to obtain derivatives of this cell line that stably expressed relatively high levels of an exogenous cyclin D1 cDNA. These derivatives displayed an increased doubling time, decreased saturation density, decreased cloning efficiency, decreased anchorage-independent growth, an increased fraction of cells in the S-phase, and decreased tumorigenicity. Thus, increased expression of cyclin D1 in this cell line markedly inhibits rather than enhances growth, which may be due to the prolongation of S-phase.
authors.affiliation: Columbia-Presbyterian Cancer Center, Columbia University, College of Physicians and Surgeons, New York, New York 10032.
authors.forename: E K
authors.initials: EK
authors.lastname: Han
authors.forename: A
authors.initials: A
authors.lastname: Sgambato
authors.forename: W
authors.initials: W
authors.lastname: Jiang
authors.forename: Y J
authors.initials: YJ
authors.lastname: Zhang
authors.forename: R M
authors.initials: RM
authors.lastname: Santella
authors.forename: Y
authors.initials: Y
authors.lastname: Doki
authors.forename: A M
authors.initials: AM
authors.lastname: Cacace
authors.forename: I
authors.initials: I
authors.lastname: Schieren
authors.forename: I B
authors.initials: IB
authors.lastname: Weinstein
mesh_terms: D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D002455:Cell Division; D002460:Cell Line; D019938:Cyclin D1; D016213:Cyclins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D015513:Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D016196:S Phase
chemical_list: D016213:Cyclins; D015513:Oncogene Proteins; D018809:Proliferating Cell Nuclear Antigen; D019938:Cyclin D1