Linked Life Data

11410520

Source:http://linkedlifedata.com/resource/pubmed/id/11410520

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2001-6-18
pubmed:abstractText
Genistein, a soy metabolite, is a potential chemopreventive agent against various types of cancer. There are several studies documenting molecular alterations leading to cell cycle arrest and induction of apoptosis in a variety of cancer cells; however, no studies, to date, have shown the effect of genistein in isogenic normal and malignant breast epithelial cells. In this study, we investigated whether genistein shows any differential sensitivity to normal (MCF10A and MCF12A) and malignant (MCF10CA1a and MDA-MB-231) breast epithelial cells. We found that genistein causes a greater degree of G(2)-M arrest and induces apoptosis in malignant cell lines compared with normal breast epithelial cells. After genistein treatment, flow cytometric analysis revealed a hyperdiploid population in malignant cells that was not observed in normal cells. Cell cycle regulator p21(WAF1), which is known to be up-regulated by genistein treatment, was greatly induced at RNA and protein levels in normal cells, whereas its level was only slightly induced in malignant MDA-MB-231 cells and not detectable in malignant MCF10CA1a cells. Therefore, we investigated the causal role of p21(WAF1) in the differential sensitivity of genistein among these cell lines. We examined the effects of genistein on p21(WAF1) -/- and p21(WAF1) +/+ HCT116 cells, which were used as controls prior to studies on breast cancer cells. We found that there was a greater degree of cell cycle arrest and apoptosis in p21(WAF1) -/- cells compared with p21(WAF1) +/+ HCT116 cells after genistein treatment. Flow cytometric analysis after genistein treatment showed a significant number of p21(WAF1) -/- cells in the hyperdiploid population, which are probably programmed to die through apoptotic processes. To further confirm the causal role of p21(WAF1) in genistein-mediated cell cycle arrest and apoptosis, we down-regulated p21(WAF1) by antisense p21(WAF1) cDNA transfection experiments. We found that both normal and malignant p21(WAF1) antisense (AS)-expressing clones became more sensitive to G(2)-M arrest after genistein treatment. Flow cytometric analysis showed an increase in the hyperdiploid population in the AS clones. Further evaluation showed an increase in apoptosis in malignant AS clones but not in normal breast epithelial AS clones. These results suggest that p21(WAF1) may play an important role in determining the sensitivity of normal and malignant breast epithelial cells to genistein.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1078-0432
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1782-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11410520-Antineoplastic Agents, pubmed-meshheading:11410520-Apoptosis, pubmed-meshheading:11410520-Blotting, Northern, pubmed-meshheading:11410520-Blotting, Western, pubmed-meshheading:11410520-Breast Neoplasms, pubmed-meshheading:11410520-Cell Cycle, pubmed-meshheading:11410520-Cell Line, pubmed-meshheading:11410520-Cyclin-Dependent Kinase Inhibitor p21, pubmed-meshheading:11410520-Cyclins, pubmed-meshheading:11410520-DNA, Complementary, pubmed-meshheading:11410520-Diploidy, pubmed-meshheading:11410520-Dose-Response Relationship, Drug, pubmed-meshheading:11410520-Down-Regulation, pubmed-meshheading:11410520-Epithelial Cells, pubmed-meshheading:11410520-Flow Cytometry, pubmed-meshheading:11410520-Genistein, pubmed-meshheading:11410520-Humans, pubmed-meshheading:11410520-Luciferases, pubmed-meshheading:11410520-Neoplasm Metastasis, pubmed-meshheading:11410520-Promoter Regions, Genetic, pubmed-meshheading:11410520-RNA, pubmed-meshheading:11410520-Transfection, pubmed-meshheading:11410520-Tumor Cells, Cultured, pubmed-meshheading:11410520-Up-Regulation
pubmed:year
2001
pubmed:articleTitle
Differential sensitivity of normal and malignant breast epithelial cells to genistein is partly mediated by p21(WAF1).
pubmed:affiliation
Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't