Human papillomavirus type 16 E7 alleviates a proliferation block in early passage human mammary epithelial cells.
Human mammary epithelial cells (HMEC) isolated from reduction mammoplasty tissue are proliferative for several passages but then enter a period termed ¿selection' or M0 during which the majority of the cells become larger, flattened, and less proliferative. Early passage HMEC (prior to M0) were transduced with human papillomavirus type-16 E6, E7, or E6/E7 by using recombinant retroviral vectors. E7 alone or E6/E7, but not E6 alone, alleviated the M0 proliferation block, suggesting a possible role for Rb or Rb-related proteins, but not p53, in M0. In addition, cells in M0 did not have increased levels of p53 or p21 proteins, further indicating that induction of these proteins is not required for the M0 proliferation block. Early passage cells contained Rb which was primarily hyperphosphorylated while cells in M0 contained Rb protein which was predominantly underphosphorylated. Cells in M0 accumulated in G1 or B0 and expressed reduced levels of cyclin A and CDK2 proteins.
Foster
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SA
Cancer Biology Program, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104, USA.
Galloway
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DA
D000818:Animals; D001940:Breast / Q000166:cytology* / Q000821:virology*; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D051357:Cyclin-Dependent Kinase 2; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000235:genetics; D016213:Cyclins / Q000235:genetics; D004847:Epithelial Cells; D005260:Female; D016193:G1 Phase / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D050725:Papillomavirus E7 Proteins; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012097:Repressor Proteins; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; C059731:oncogene protein E7, Human papillomavirus type 16; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases