* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Exporter la page en pdf
Vectors in gene therapy wikipedia , lookup
Therapeutic gene modulation wikipedia , lookup
Epigenetics of depression wikipedia , lookup
Epigenetics of human development wikipedia , lookup
RNA silencing wikipedia , lookup
Polycomb Group Proteins and Cancer wikipedia , lookup
Epigenetics in learning and memory wikipedia , lookup
Nicotinic acid adenine dinucleotide phosphate wikipedia , lookup
Epigenetics of neurodegenerative diseases wikipedia , lookup
Long non-coding RNA wikipedia , lookup
Gene therapy of the human retina wikipedia , lookup
Non-coding RNA wikipedia , lookup
Point mutation wikipedia , lookup
Oncogenomics wikipedia , lookup
Gene expression profiling wikipedia , lookup
Nutriepigenomics wikipedia , lookup
Site-specific recombinase technology wikipedia , lookup
Messenger RNA wikipedia , lookup
Primary transcript wikipedia , lookup
Team Publications Molecular Oncology Year of publication 2005 Claire Dunois-Lardé, Olivier Levrel, Aude Brams, Jean Paul Thiery, François Radvanyi (2005 Feb 4) Absence of FGFR3 mutations in urinary bladder tumours of rats and mice treated with N-butyl-N-(-4-hydroxybutyl)nitrosamine. Molecular carcinogenesis : 142-9 Summary Frequent activating mutations of FGFR3 (fibroblast growth factor receptor 3) are found in human urothelial cell carcinomas, particularly in superficial papillary tumours (in 74%-84% of pTaG1-G2), but not in carcinomas in situ (CIS) and at a low rate in invasive tumours (in 16%-21% of pT1-4). In mice and rats, BBN (N-butyl-N-(4-hydroxybutyl)nitrosamine) specifically induces bladder tumours. In rats, superficial papillary tumours are mostly observed. In mice, tumour progression follows the CIS pathway: CIS are first observed, followed by tumours that invade surrounding muscle. Therefore, we looked for FGFR3 mutations in these two animal models of bladder cancer. Only the FGFR3b isoform is expressed in human urothelium and derived tumours. We identified the FGFR3b isoform in rats for the first time and showed that this is the main isoform expressed in the bladder urothelium and derived carcinomas in mice and rats, as in humans. SSCP and sequence analysis of FGFR3b showed sequence changes (polymorphisms or silent mutations) in four BBN-induced rat and mouse bladder tumours. The absence of activating mutations of FGFR3 in the mouse model was in agreement with the fact that mouse BBN-induced bladder tumour progression mimics the CIS pathway. The absence of FGFR3 mutations in the rat bladder tumours suggests that, at least at the genetic level, rat superficial papillary tumours differ from their human counterparts. Year of publication 2004 Isabelle Bernard-Pierrot, David Ricol, Andrew Cassidy, Alexander Graham, Paul Elvin, Aurélie Caillault, Séverine Lair, Philippe Broët, Jean-Paul Thiery, François Radvanyi (2004 Nov 2) Inhibition of human bladder tumour cell growth by fibroblast growth factor receptor 2b is independent of its kinase activity. Involvement of the carboxyterminal region of the receptor. Oncogene : 9201-11 Summary The b isoform of fibroblast growth factor receptor 2, FGFR2b/FGFR2-IIIb/Ksam-IIC1/KGFR, a tyrosine kinase receptor, is expressed in a wide variety of epithelia and is downregulated in several human carcinomas including prostate, salivary and urothelial cell carcinomas. FGFR2b has been shown to inhibit growth in tumour cell lines derived from these carcinomas. Here, we investigated the molecular mechanisms underlying the inhibition of human urothelial carcinoma cell growth following FGFR2b expression. Using a nylon DNA INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 1 Team Publications Molecular Oncology array, we analysed the gene expression profile of the T24 bladder tumour cell line, transfected or not with a construct encoding FGFR2b. The expression of FGFR2b in T24 cells decreased insulin-like growth factor (IGF)-II mRNA levels. This decrease was correlated with a decrease in IGF-II secretion and may have been responsible for the observed inhibition of cell growth because the addition of exogenous IGF-II restored growth rates to normal levels. Using SU5402, an inhibitor of FGFR tyrosine kinase activity, and a kinase dead mutant of the receptor, FGFR2b Y659F/Y660F, we also demonstrated that the growth inhibition and decrease in IGF-II secretion induced by FGFR2b did not require tyrosine kinase activity. Finally, we demonstrated the involvement of the distal carboxy-terminal domain of the receptor in decreasing IGF-II expression and inhibiting T24 cell growth, as Ksam-IIC3, a variant of FGFR2b carrying a short carboxy-terminus, neither downregulated IGF-II nor inhibited cell proliferation. Our data suggest that FGFR2b inhibits the growth of bladder carcinoma cells by reducing IGF-II levels via its carboxy-terminal domain, independent of its tyrosine kinase activity. Anna Almeida, Jean Paul Thiery, Henri Magdelénat, François Radvanyi (2004 Apr 29) Gene expression analysis by real-time reverse transcription polymerase chain reaction: influence of tissue handling. Analytical biochemistry : 101-8 Summary Factors such as warm ischemia and time at room temperature before tissue treatment may influence the results of mRNA expression analyses on tissue specimens obtained during surgery. We evaluated the effect of these factors on RNA integrity and mRNA expression levels by incubating freshly obtained mouse liver tissue at 25 or 37 degrees C for periods of 0-4 h. Changes in the mRNA expression levels of seven genes, Tbp, Eef1a, Fos, Junb, Myc, Vegf, and Glut2, were determined by real-time reverse transcription-polymerase chain reaction. Incubation at 25 degrees C for up to 4 h only slightly altered (by a factor of less than 2) levels of mRNA for Tbp, Eef1a, Junb, Myc, Vegf, and Glut2. This result is consistent with limited RNA degradation at this temperature. Incubation at 37 degrees C strongly affected the levels of these mRNAs. Four hours of incubation at this temperature resulted in extensive RNA degradation, with mRNA levels falling to 1/10th those before incubation. When relative quantification was performed, i.e., quantification of the target gene transcripts in comparison to an endogenous housekeeping transcript (Tbp or Eef1a), the changes in mRNA levels were reduced to less than 2.5-fold. Fos behaved very differently from the other genes tested on incubation, with Fos mRNA levels increasing considerably following incubation at either 25 or 37 degrees C. Our data suggest that, with the exception of certain genes induced by tissue injury, relative quantification of mRNA, even on degraded RNA samples, can provide a reliable estimate of in vivo mRNA levels. INSTITUT CURIE, 20 rue d’Ulm, 75248 Paris Cedex 05, France | 2