Biomedical subjects

Bruno Lectard

Publications and source records attributed to Bruno Lectard.

3 recordsLinked to original sources

PubMed2006

Transcriptional response of wild-type and ataxia telangiectasia lymphoblasts following exposure to equitoxic doses of ionizing radiation.

Experiments were designed to compare the transcriptional response to ionizing radiation (IR) of wild-type (WT) and ataxia telangiectasia (AT) cells. mRNA levels were assessed 2, 4 and 24 h after exposure to equitoxic doses using cDNA microarrays. Data reveal distinct patterns of gene expression between AT and WT cells since IR-responsive genes were mostly cell-type specific, this group representing 87 and 94% of the responding genes in WT and AT cells, respectively. In both cell lines, transcriptional alterations of genes associated with proliferation correlated with the observed cell cycle and growth data. Deregulated genes involved in apoptosis suggest that wild-type cells were more prone to cell death by apoptosis than AT cells. Furthermore, genes associated with the response to oxidative stress were particularly deregulated in wild-type cells whereas alterations of genes related to unexpected pathways including RNA processing, protein synthesis and lipid metabolism were specifically found in irradiated AT cells. These data suggest that under radiation conditions leading to a similar survival of WT and AT cells, the mechanisms triggered after radiation were mainly dependent on ATM status and thus on the intrinsic radiosensitivity.

Ataxia Telangiectasia↗

PubMed2004

Progesterone prevents radiation-induced apoptosis in breast cancer cells.

Sex steroid hormones play an essential role in the control of homeostasis in the mammary gland. Although the involvement of progesterone in cellular proliferation and differentiation is well established, its exact role in the control of cell death still remains unclear. As dysregulation of the apoptotic process plays an important role in the pathogenesis of breast cancer, we investigated the regulation of apoptosis by progesterone in various breast cancer cell lines. Our results show that progesterone treatment protects against radiation-induced apoptosis. This prevention appears to be mediated by the progesterone receptor and is unrelated to p53 status. There is also no correlation with the intrinsic hormonal effect on cell proliferation, as the presence of cells in a particular phase of the cell cycle. Surprisingly, progesterone partly allows bypassing of the irradiation-induced growth arrest in G(2)/M in PgR+ cells, leading to an increase in cell proliferation after irradiation. One consequence of this effect is a higher rate of chromosome damage in these proliferating progesterone-treated cells compared to what is observed in untreated irradiated cells. We propose that progesterone, by inhibiting apoptosis and promoting the proliferation of cells with DNA damage, potentially facilitates the emergence of genetic mutations that may play a role in malignant transformation.

Apoptosis↗

PubMed2003

In vitro aging of rat lung cells. Downregulation of telomerase activity and continuous decrease of telomere length are not incompatible with malignant transformation.

Most normal mammalian somatic cells cultivated in vitro enter replicative senescence after a finite number of divisions, as a consequence of the progressive shortening of telomeres during proliferation that reflects one aspect of organism/cellular aging. The situation appears more complex in rodent cells due to physiological telomerase expression in most somatic normal tissues, great telomere length, and the difficulties of finding suitable in vitro culture conditions. To study in vitro aging of rat lung epithelial cells, we have developed primary culture conditions adapted to rat fresh lung explants and have studied for 1 year (50 passages) the changes in cellular proliferation and mortality, genetic instability, telomerase activity, telomere length, and tumorigenic potential. We have observed an absence of senescence and/or crisis, a transient genetic instability, the persistence of a differentiated Clara cell phenotype, a steady decrease in telomerase activity followed by a low residual activity together with a continuous decrease in telomere length, a constant rate of proliferation, and the acquisition of tumorigenic potential. The bypass of the growth arrest and the acquisition of long-term growth properties could be explained by the loss of p16(INK4a) expression, the ARF/p53 pathway not being altered. In conclusion, these results clearly indicate that, in rat lung epithelial cells, in vitro transformation and acquisition of tumorigenic properties can occur even if the telomere length is still decreasing and telomerase activity remains downregulated.

Animals↗