Cytotoxicity of a Novel Fibroblast Growth Factor Receptor Targeted Immunotoxin on a Human Ovarian Teratocarcinoma Cell Line

2006 ◽  
Vol 21 (4) ◽  
pp. 321-332 ◽  
Author(s):  
Huajie Zhang ◽  
Shumin Zhang ◽  
Hui Zhuang ◽  
Fengmin Lu
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Cell Line ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Fibroblast Growth ◽  
Teratocarcinoma Cell ◽  
Teratocarcinoma Cell Line

scholarly journals A Novel Chromosomal Translocation t(4; 14)(p16.3; q32) in Multiple Myeloma Involves the Fibroblast Growth-Factor Receptor 3 Gene

Blood ◽  
1997 ◽  
Vol 90 (10) ◽  
pp. 4062-4070 ◽  
Author(s):  
Raffaella Richelda ◽  
Domenica Ronchetti ◽  
Luca Baldini ◽  
Lilla Cro ◽  
Luigi Viggiano ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Cell Line ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Chromosomal Translocation ◽  
Chromosomal Translocations ◽  
Fibroblast Growth ◽  
Fgfr3 Gene

Abstract Chromosomal translocations involving the immunoglobulin heavy chain (IGH) locus at chromosome 14q32 represent a common mechanism of oncogene activation in lymphoid malignancies. In multiple myeloma (MM), the most consistent chromosomal abnormality is the 14q+ marker, which originates in one third of cases through a t(11; 14)(q13; q32) chromosomal translocation; in the remaining cases, the identity of the partner chromosomes has not been well established. We used a Southern blot approach based on the linkage analysis of the joining (J) and the constant (C) μ, α, and γ regions to detect cases bearing IGH switch-mediated chromosomal translocations. We evaluated DNA of 88 nonkaryotyped patients with MM (78 cases) or plasma cell leukemia (PCL) (10 cases) and found the presence of “illegitimate” rearranged IGH fragments (no comigration between the J and C regions) in 21 cases. To confirm this analysis, we cloned the illegitimate rearranged fragments from three samples, and the molecular and fluorescent in situ hybridization (FISH) analyses indicated the presence of chromosomal translocations juxtaposing a switch IGH region to sequences from chromosomes 11q13 (one PCL case) or 4p16.3 (two MM cases). Interestingly, the breakpoints on 4p16.3 occurred about 14 kb apart in a genomic region located approximately 50 kb centromeric to the fibroblast growth-factor receptor 3 (FGFR3) gene. Moreover, Southern blot analysis using 4p16.3 genomic probes detected a rearrangement in an additional MM tumor. FISH analysis of the MM-derived KMS-11 cell line, reported to be associated with a t(4; 14)(p16.3; q32), showed that the FGFR3 gene was translocated on 14q32. High levels of FGFR3 mRNA expression were observed in the cloned MM tumors and KMS-11 cell line, but not in the cases that were apparently negative for this lesion. Furthermore, a point mutation at codon 373 in the transmembrane domain of the FGFR3 gene resulting in an amino acid substitution (Tyr → Cys) was detected in the KMS-11 cell line. These findings indicate that the t(4; 14)(p16.3; q32) represents a novel, recurrent chromosomal translocation in MM, and suggest that the FGFR3 gene may be the target of this abnormality and thus contribute to tumorigenesis in MM.

scholarly journals Overexpression of fibroblast growth factor receptor 3 in a human thyroid carcinoma cell line results in overgrowth of the confluent cultures

1999 ◽  
pp. 169-173 ◽  
Author(s):  
H Onose ◽  
N Emoto ◽  
H Sugihara ◽  
K Shimizu ◽  
I Wakabayashi
Keyword(s):  
Growth Factor ◽  
Thyroid Carcinoma ◽  
Fibroblast Growth Factor ◽  
Cell Line ◽  
Fibroblast Growth Factor Receptor ◽  
Carcinoma Cell ◽  
Growth Factor Receptor ◽  
Fibroblast Growth ◽  
Papillary Thyroid ◽  
Thyroid Carcinoma Cell

Recent reports indicate that a gain-of-function mutation in fibroblast growth factor receptor 3 (FGFR-3) inhibits cell growth in the cartilaginous growth plates. These results suggest that FGFR-3 may be the receptor transducing growth inhibitory signals. Using reverse transcription-PCR we examined seven papillary thyroid carcinomas to determine FGFR-3 expression. Six out of the seven papillary carcinomas expressed FGFR-3. To clarify the role of FGFR-3 in thyroid carcinoma, FGFR-3 was overexpressed in an established human papillary thyroid carcinoma cell line. High levels of FGFR-3 protein were identified in cells stably transfected with the vector containing FGFR-3 cDNA. The specific binding of 125I-FGF-2 of these cells was threefold higher than that of control cells. Growth rates of cells overexpressing FGFR-3 were similar to those of control cells. However, cells overexpressing FGFR-3 continued to grow beyond the density at which control cells stopped proliferating. These results suggest that FGFR-3 in thyroid carcinoma is not involved strongly in the cell proliferation mechanism but may contribute to the malignant extension of some of the carcinomas by modifying cell contact signaling.

scholarly journals An Intronic Sequence Element Mediates Both Activation and Repression of Rat Fibroblast Growth Factor Receptor 2 Pre-mRNA Splicing

1998 ◽  
Vol 18 (4) ◽  
pp. 2205-2217 ◽  
Author(s):  
Russ P. Carstens ◽  
Wallace L. McKeehan ◽  
Mariano A. Garcia-Blanco
Keyword(s):  
Prostate Cancer ◽  
Alternative Splicing ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Cell Line ◽  
Cancer Cell ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Fibroblast Growth ◽  
Sequence Element

ABSTRACT Alternative splicing of fibroblast growth factor receptor 2 (FGF-R2) is an example of highly regulated alternative splicing in which exons IIIb and IIIc are utilized in a mutually exclusive manner in different cell types. The importance of this splicing choice is highlighted by studies which indicate that deregulation of the FGF-R2 splicing is associated with progression of prostate cancer. Loss of expression of a IIIb exon-containing isoform of FGF-R2 [FGF-R2 (IIIb)] accompanies the transition of a well-differentiated, androgen-dependent rat prostate cancer cell line, DT3, to the more aggressive, androgen-independent AT3 cell line. We have used transfection of rat FGF-R2 minigenes into DT3 and AT3 cancer cell lines to study the mechanisms that control alternative splicing of rat FGF-R2. Our results support a model in which an importantcis-acting element located in the intron between these alternative exons mediates activation of splicing using the upstream IIIb exon and repression of the downstream IIIc exon in DT3 cells. This element consists of 57 nucleotides (nt) beginning 917 nt downstream of the IIIb exon. Analysis of mutants further demonstrates that an 18-nt “core sequence” within this element is most crucial for its function. Based on our observations, we have termed this sequence element ISAR (for intronic splicing activator and repressor), and we suggest that factors which bind this sequence are required for maintenance of expression of the FGF-R2 (IIIb) isoform.

Sign in / Sign up

Export Citation Format

Share Document