Linked Life Data

11929841

Source:http://linkedlifedata.com/resource/pubmed/id/11929841

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2002-4-3
pubmed:abstractText
bcl-xL is a M(r) 26,000 bcl-2 homologue that is highly expressed in prostate cancer cells. In previous studies, the down-regulation of its expression by antisense oligonucleotides led to resistance. In this work, the 445-bp 5' terminus of the bcl-xL cDNA was cloned in the antisense orientation and stably transfected into DU145 and LNCaP prostate cancer cells. In the DU145 (and to a lesser extent the LNCaP) transfectants, phenotypic changes (versus mock-transfected cells) included an increase in doubling time (from 36 to 175 h) in the clone in which bcl-xL protein expression was 25% of control. The transfectants did not demonstrate characteristic apoptotic changes, as demonstrated by 4',6-diamidino-2-phenylindole staining, lack of either DNA laddering, caspase-3 activation, or poly(ADP)ribose and lamin cleavage, and the absence of a significant sub-G(0) population. Cell cycle analysis demonstrated an increase in a tetraploid population (from 28% to 66%), as well as the appearance of a hypertetraploid population. Levels of cIAP-1 protein were almost undetectable in the mock cells but increased at least 25-fold in the DU145 transfectants. The down-regulation of bcl-xL in both DU145 (and to a much lesser extent in LNCaP) cells led to their resistance to cytotoxic agents, including docetaxel, mitoxantrone, etoposide, vinblastine, and carboplatin. Reversion of bcl-xL expression in stable DU145 transfectants to nearly the levels found in the mock-transfected cells was accomplished by retroviral infection of the cells with a bcl-xL sense cDNA under control of a prolific promoter. This led to a dramatic increase in the growth rate and in BrdUrd incorporation, as well as a sharp decrease in the expression of cIAP-1 protein. Overall, these findings highlight the adaptability of prostate cancer cells to loss of bcl-xL and suggest that in addition to its prosurvival role, bcl-xL protein may also be involved in the regulation of the rate of cellular proliferation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
62
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2175-83
pubmed:dateRevised
2008-5-14
pubmed:meshHeading
pubmed-meshheading:11929841-Antineoplastic Agents, pubmed-meshheading:11929841-Apoptosis, pubmed-meshheading:11929841-Cell Division, pubmed-meshheading:11929841-DNA, Neoplasm, pubmed-meshheading:11929841-Down-Regulation, pubmed-meshheading:11929841-Drug Resistance, Multiple, pubmed-meshheading:11929841-Drug Resistance, Neoplasm, pubmed-meshheading:11929841-Humans, pubmed-meshheading:11929841-Male, pubmed-meshheading:11929841-Ploidies, pubmed-meshheading:11929841-Prostatic Neoplasms, pubmed-meshheading:11929841-Protein Biosynthesis, pubmed-meshheading:11929841-Proteins, pubmed-meshheading:11929841-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:11929841-RNA, Antisense, pubmed-meshheading:11929841-Transfection, pubmed-meshheading:11929841-X-Linked Inhibitor of Apoptosis Protein, pubmed-meshheading:11929841-bcl-X Protein
pubmed:year
2002
pubmed:articleTitle
Antisense RNA down-regulation of bcl-xL Expression in prostate cancer cells leads to diminished rates of cellular proliferation and resistance to cytotoxic chemotherapeutic agents.
pubmed:affiliation
Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA.
pubmed:publicationType
Journal Article