Overrepresentation of 7q31 and 17q in renal cell carcinomas

Glukhova, Liubov; Goguel, A; Chudoba, Ilse; Angevin, Eric; Pavon, Christine; Terrier‐Lacombe, Marie‐José; Meddeb, Mounira; Escudier, Bernard; Bernheim, Alain

doi:10.1002/(sici)1098-2264(199807)22:3<171::aid-gcc2>3.3.co;2-k

Cited by 4 publications

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“…The availability of a RCC xenograft model in immunodeficient mice 23,24 will permit validation of this method in vivo. Further studies will focus mainly on gene targeting to metastases, which continues to be one of the major issues in cancer gene therapy.…”

Section: Discussionmentioning

confidence: 99%

“…23,24 In vitro establishment and the characterization of RCC lines were performed as described previously. 25 Cells were grown at 37°C under 5% CO 2 in Dulbecco's modified Eagle's medium with glutamax-1 (Life Technologies, Paisley, UK) supplemented with 10% fetal calf sera (Seromed, Berlin, Germany), 5% nonessential amino acids, 10 mM sodium pyruvate (Life Technologies), and penicillin (10 U/mL)/streptomycin (10 mg/mL) (Seromed).…”

Section: Cellsmentioning

confidence: 99%

“…The expression of G250 TAA was studied on the human RCC lines, which were characterized as described previously, 23,24 by flow cytometry analysis. As shown in Figure 1, G250 TAA expression was highly positive on the IGR/RCC-58 and IGR/RCC-40 lines and negative on the IGR/RCC-17 and IGR/RCC-47 lines.…”

Section: Expression Of G250 Antigen On Rcc Linesmentioning

confidence: 99%

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Antibody-mediated endocytosis of G250 tumor-associated antigen allows targeted gene transfer to human renal cell carcinoma in vitro

et al. 1999

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Specific gene transfer into targeted tumor cells remains a critical issue for the development of systemic gene therapy protocols. With this end in view, we have tested the possibility of selectively directing genes to tumor cells through the recognition of tumor-associated antigens (TAA). This was approached in vitro on four human renal cell carcinoma (RCC) lines by means of the highly specific mouse G250 monoclonal antibody (mAb) chemically conjugated to a plasmid DNA conveying a reporter activity. This mAb directed to a TAA that is present on 95% of primary RCCs and on 60% of metastatic human RCCs was extensively characterized, including during clinical trials. Epifluorescence microscopy analysis indicated that upon specific binding to G250 TAA, G250 mAb alone or conjugated to plasmid DNA was internalized by an active endocytic process and colocalized with the transferrin concentrated in the late recycling perinuclear compartment. We also observed that both unconjugated G250 mAb or G250 mAb conjugated to plasmid DNA remained in the perinuclear region of the cells for Ն20 hours and were not rapidly translocated to lysosomes or recycled to the plasma membrane. In contrast, unconjugated plasmid DNA was not internalized. After transfection of G250 TAA-positive RCC lines with G250 mAb conjugated to a plasmid cDNA encoding mouse interleukin-2, a significant and sustained production of mouse interleukin-2 protein was detected from days 5-15 and was abrogated by inhibiting the internalization process. Altogether, our data showed that endocytosis of G250 TAA should be the basis of gene transfer to RCC, suggesting that targeting of TAA capable of internalization may be the basis of new approaches for designing alternative cancer gene therapy procedures.Key words: Renal cell carcinoma; tumor-associated antigen; endocytosis; antifection; gene therapy.M ost ongoing clinical trials in cancer gene therapy are based primarily on direct intratumoral administration of recombinant vectors and/or on ex vivo cell manipulations. 1 To date, only a few procedures permit cell-or tissue-specific targeting in vivo. This can be achieved with specific viral-based gene delivery systems 2,3 and nonviral approaches through DNA complexed to a ligand capable of binding the surface molecules expressed on the targeted cells. 4 -6 We have developed an approach named antifection that allows specific gene targeting. This technique is based on the use of antibodies (Abs) directed toward cell-specific receptors, which are chemically conjugated to plasmid DNA. This was first validated by using various reporter genes expressed in lymphoid cells, both in vitro and in vivo. 7,8 Recently, we have also reported the successful transfer of interleukin-3 (IL-3)-encoding plasmid DNA linked to anti-CD117 Abs into cultured human primary hemopoietic progenitors. 9 Although most of the ligands examined so far continue to be expressed on nontumor cells, limiting the tumor targeting, several Abs directed to tumor-associated antigen (TAA) present a widely restricted...

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Section: Discussionmentioning

confidence: 99%

Section: Cellsmentioning

confidence: 99%

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Antibody-mediated endocytosis of G250 tumor-associated antigen allows targeted gene transfer to human renal cell carcinoma in vitro

et al. 1999

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“…These tumors commonly exhibit a number of chromosomal abnormalities including tetrasomy of chromosome 7, trisomy of chromosomes 10, 12, 16 and 17, and/or loss of the Y chromosome (van den Berg et al, 1997). Overexpression of genes located on these chromosomes has been suggested to contribute to the development of papillary renal cell carcinomas (Glukhova et al, 1998). Another subset of these tumors show abnormalities in the chromosome Xp11 region that contains the gene for the transcription factor, TFE3.…”

Section: Introductionmentioning

confidence: 99%

PSF-TFE3 oncoprotein in papillary renal cell carcinoma inactivates TFE3 and p53 through cytoplasmic sequestration

2003

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Papillary renal cell carcinomas are associated with chromosomal translocations involving the helix-loophelix leucine-zipper region of the TFE3 gene on the X chromosome. These translocations lead to the expression of TFE3 chimeras of PRCC, RCC17, NonO and PSF (PTB-associated splicing factor). In this study, we explored the role of PSF-TFE3 fusion protein in mediating cell transformation. Unlike wild-type TFE3 or PSF, which are nuclear proteins, PSF-TFE3 is not a nuclear protein and is targeted to the endosomal compartment. Although PSF-TFE3 has no effect on the nuclear localization of wild-type PSF, it sequesters wildtype TFE3 as well as p53 in the extranuclear compartment leading to functionally null p53 and TFE3 cells. In UOK-145 papillary renal carcinoma cells, which endogenously express PSF-TFE3, siRNA complementary to the PSF-TFE3 fusion junction leads to a reduction in PSF-TFE3 and redistribution of endogenous TFE3 and p53 from the cytoplasmic compartment to the nucleus. Our results indicate that PSF-TFE3 acts through a novel mechanism, and exports TFE3, p53 and possibly other factors from the nucleus to the cytoplasm for degradation leading to the transformed phenotype. Thus, PSF-TFE3 is a promising target for the treatment for a subset of renal cell carcinomas.

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“…In both cases, all the minichromosomes were composed of small fragments derived solely from chromosome 7. Moreover, the der(7) minichromosomes from both tumours appeared to only have in common a small region located within band 7q31 (Glukhova et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Mapping of the 7q31 subregion common to the small chromosome 7 derivatives from two sporadic papillary renal cell carcinomas: increased copy number and overexpression of the MET proto-oncogene

et al. 2000

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Overrepresentation of 7q31 and 17q in renal cell carcinomas

Cited by 4 publications

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Antibody-mediated endocytosis of G250 tumor-associated antigen allows targeted gene transfer to human renal cell carcinoma in vitro

Antibody-mediated endocytosis of G250 tumor-associated antigen allows targeted gene transfer to human renal cell carcinoma in vitro

PSF-TFE3 oncoprotein in papillary renal cell carcinoma inactivates TFE3 and p53 through cytoplasmic sequestration

Mapping of the 7q31 subregion common to the small chromosome 7 derivatives from two sporadic papillary renal cell carcinomas: increased copy number and overexpression of the MET proto-oncogene

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