Retinoblastoma function is a better indicator of cellular phenotype in cultured breast adenocarcinoma cells than retinoblastoma expression.
Loss of or lowered retinoblastoma (Rb) expression has been included as a prognostic indicator in breast cancer. Low or no Rb expression is seen most commonly in high-grade breast adenocarcinomas, suggesting that a relationship may exist between loss of Rb and a less differentiated state, high proliferation rate, and high metastatic potential. In this study, we compared Rb function in two established breast adenocarcinoma cell lines, MCF-7 and MDA-MB-231, and in an established immortalized mammary epithelial cell line, MCF10A. Cells were synchronized in G0/G1 and were released for several durations, at which time total Rb protein, mRNA, and Rb/E2F/DNA complex formation were evaluated. Rb protein was significantly higher in the tumor cells than in MCF10A cells. However, Rb function was high for a longer duration in MCF10A cells as compared with MCF-7 and MDA-MB-231 cells. Our data support the general conclusion that Rb function, but not necessarily Rb protein, is lower in highly malignant breast adenocarcinoma cells as compared with lower grade tumor cells. These results emphasize the relevance of assessing Rb function over Rb protein. This is particularly important if Rb is to be used as a prognostic indicator for breast adenocarcinoma.
Botos
Jeannine
J
Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, USA. Botosjea@exchange.nih.gov
Smith
Roger
R
Kochevar
Deborah T
DT
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D001483:Base Sequence; D001940:Breast / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D018797:Cell Cycle Proteins; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008969:Molecular Sequence Data; D010641:Phenotype; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured
D018797:Cell Cycle Proteins; D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D014157:Transcription Factors