Linked Life Data

15361849

Source:http://linkedlifedata.com/resource/pubmed/id/15361849

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
52
pubmed:dateCreated
2004-11-4
pubmed:abstractText
Abnormalities in the expression of the tumour suppressor fragile histidine triad (FHIT) gene have been reported in a variety of human tumours, including lung cancer and restoration of its expression in cancer cell lines resulted in the inhibition of proliferation and apoptosis induction. Most of the studies that have assigned a proapoptotic role to the FHIT gene were performed in adenoviral-FHIT-transduced cancer cells expressing high levels of the Fhit protein. The present work was the first study designed to investigate the effects of FHIT gene replacement in a human FHIT-negative non-small-cell lung cancer (NSCLC) cell line (Calu-1) by using a hormone-inducible expression system that allows tight modulation of the transgene expression. Through this approach, we demonstrated that a prolonged induction was required to accumulate the Fhit protein at levels adequate to promote a significant decrease of cell proliferation. Analysis of cell-cycle phase distribution showed an accumulation of cells in the G0/G1 phase and a concomitant decrease in the S phase. Moreover, an upregulation of p21waf1 transcript was found, which could account for the alteration of the cycling properties of the cells. The growth-inhibitory effects observed were not associated with apoptosis appearance, and although in these conditions the Fhit protein content was higher than in normal bronchial human epithelial cells (NHBE), it was still significantly lower than the level capable of inducing apoptosis in Calu-1 cells after adenoviral-mediated FHIT gene transfer. These results indicate that the tumour suppressor properties of Fhit are strictly related to its expression level and show that the Fhit protein has a dose-dependent antiproliferative effect on the Fhit-negative Calu-1 lung cancer cell line.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
4
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8439-46
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Dose-dependent effect of FHIT-inducible expression in Calu-1 lung cancer cell line.
pubmed:affiliation
Department of Experimental Medicine, University of Parma, via Volturno 39, Parma 43100, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't