RÉSUMÉ
The correct identification of all human genes, and their derived transcripts, has not yet been achieved, and it remains one of the major aims of the worldwide genomics community. Computational programs suggest the existence of 30,000 to 40,000 human genes. However, definitive gene identification can only be achieved by experimental approaches. We used two distinct methodologies, one based on the alignment of mouse orthologous sequences to the human genome, and another based on the construction of a high-quality human testis cDNA library, in an attempt to identify new human transcripts within the human genome sequence. We generated 47 complete human transcript sequences, comprising 27 unannotated and 20 annotated sequences. Eight of these transcripts are variants of previously known genes. These transcripts were characterized according to size, number of exons, and chromosomal localization, and a search for protein domains was undertaken based on their putative open reading frames. In silico expression analysis suggests that some of these transcripts are expressed at low levels and in a restricted set of tissues.
Sujet(s)
Humains , Animaux , Mâle , Souris , ADN complémentaire/génétique , Génome humain , Analyse de séquence d'ADN/méthodes , Testicule/composition chimique , Transcription génétique/génétique , Séquence d'acides aminés , Cartographie chromosomique , Banque de gènes , Données de séquences moléculairesRÉSUMÉ
Tamoxifen (TAM) is an antiestrogenic drug widely used in breast cancer treatment. By using the Differential Display technique in normal and malignant breast tissues, before and during TAM therapy, we were able to demonstrate that expression of the CD36 gene is down-regulated by this drug. CD36 is a cell-surface glycoprotein that acts as a receptor for thrombospondin-1, oxidized-LDL and collagens type I and IV. Thrombospondin-1 is involved in invasion, metastasis and angiogenesis and therefore the down-regulation of CD36 induced by TAM, might correspond to an alternative mechanism of action of this drug. CD36 is also one of the receptors for the oxidized-LDL which in turn is involved in pathogenesis of arteriosclerosis; thus the down-regulation of CD36 during TAM might explain the at least in part the lower levels of myocardial infarction during its use.