Identification of regulatory sequences in the promoter of the PDGF B-chain gene in malignant mesothelioma cell lines

Jan Bas Prins; Anthonie W. Langerak; Ron P.H. Dirks; Carin A.J. Van Der Linden-Van Beurden; Petronella A.J.M. De Laat; Henri P.J. Bloemers; Marjan A. Versnel

doi:10.1016/S0925-4439(96)00060-9

Identification of regulatory sequences in the promoter of the PDGF B-chain gene in malignant mesothelioma cell lines

Jan Bas Prins^*, Anthonie W. Langerak, Ron P.H. Dirks, Carin A.J. Van Der Linden-Van Beurden, Petronella A.J.M. De Laat, Henri P.J. Bloemers, Marjan A. Versnel

^*Corresponding author for this work

Immunology

Research output: Contribution to journal › Article › Academic › peer-review

5 Citations (Scopus)

Abstract

Platelet-derived growth factor (PDGF) B-chain mRNA is readily detectable in malignant mesothelioma (MM) cell lines, but not in normal mesothelial (NM) cell lines. The high affinity receptor for PDGF B-chain dimers, the PDGF β-receptor, is expressed in MM cell lines. NM cell lines predominantly, express the PDGF α-receptor. Coexpression of the PDGF β-receptor and its ligand may lead to an autocrine growth stimulating loop in the malignant cell type. In nuclear run off experiments, PDGF B-chain mRNA was detectable in MM cells only, indicating an increased level of transcription in this cell type. The proximal promoter of the PDGF B-chain gene contains DNaseI hypersensitive (DH) sites and mediates reporter gene activation in both normal and malignant cells. Nuclear proteins, extracted from bath cell types, interact with DNA sequences within the proximal promoter around bp -64 to -61 relative to the transcription start site. Electrophoretic mobility shift assays (EMSAs) indicate that these factors are more abundantly present in the malignant than in the normal cell type. A DH site around -9.9 kb was found in both cell types. When tested in CAT assays, this region exerted a stimulatory effect on transcription in malignant cells. The elevated level of transcription of the PDGF B-chain gene in malignant cells may well be the result of interaction of regulatory sites in the proximal promoter and an enhancing element located at -9.9 kb from the transcription start site.

Original language	English
Pages (from-to)	223-232
Number of pages	10
Journal	Biochimica et Biophysica Acta - Molecular Basis of Disease
Volume	1317
Issue number	3
DOIs	https://doi.org/10.1016/S0925-4439(96)00060-9
Publication status	Published - 16 Dec 1996

Bibliographical note

Funding Information:
We would like to thankp rof.dr. R. Bennera ndprof. dr. A. Hagemeijefro r continuoussu pportd, r. M. Verschuren for settingu p the EMSA technologyM, rs. E. Frankenf or technicala ssistanceM, r. T. van Os for preparingt he figuresa ndMs. P.C. Assemsf or secretariaals sistanceT.h e work describedin this paper was supportedb y a grant from the Dutch CancerS ociety.

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Prins, J. B., Langerak, A. W., Dirks, R. P. H., Van Der Linden-Van Beurden, C. A. J., De Laat, P. A. J. M., Bloemers, H. P. J., & Versnel, M. A. (1996). Identification of regulatory sequences in the promoter of the PDGF B-chain gene in malignant mesothelioma cell lines. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1317(3), 223-232. https://doi.org/10.1016/S0925-4439(96)00060-9

@article{464dfbaa2577424cb638965093d77bd4,

title = "Identification of regulatory sequences in the promoter of the PDGF B-chain gene in malignant mesothelioma cell lines",

abstract = "Platelet-derived growth factor (PDGF) B-chain mRNA is readily detectable in malignant mesothelioma (MM) cell lines, but not in normal mesothelial (NM) cell lines. The high affinity receptor for PDGF B-chain dimers, the PDGF β-receptor, is expressed in MM cell lines. NM cell lines predominantly, express the PDGF α-receptor. Coexpression of the PDGF β-receptor and its ligand may lead to an autocrine growth stimulating loop in the malignant cell type. In nuclear run off experiments, PDGF B-chain mRNA was detectable in MM cells only, indicating an increased level of transcription in this cell type. The proximal promoter of the PDGF B-chain gene contains DNaseI hypersensitive (DH) sites and mediates reporter gene activation in both normal and malignant cells. Nuclear proteins, extracted from bath cell types, interact with DNA sequences within the proximal promoter around bp -64 to -61 relative to the transcription start site. Electrophoretic mobility shift assays (EMSAs) indicate that these factors are more abundantly present in the malignant than in the normal cell type. A DH site around -9.9 kb was found in both cell types. When tested in CAT assays, this region exerted a stimulatory effect on transcription in malignant cells. The elevated level of transcription of the PDGF B-chain gene in malignant cells may well be the result of interaction of regulatory sites in the proximal promoter and an enhancing element located at -9.9 kb from the transcription start site.",

author = "Prins, {Jan Bas} and Langerak, {Anthonie W.} and Dirks, {Ron P.H.} and {Van Der Linden-Van Beurden}, {Carin A.J.} and {De Laat}, {Petronella A.J.M.} and Bloemers, {Henri P.J.} and Versnel, {Marjan A.}",

note = "Funding Information: We would like to thankp rof.dr. R. Bennera ndprof. dr. A. Hagemeijefro r continuoussu pportd, r. M. Verschuren for settingu p the EMSA technologyM, rs. E. Frankenf or technicala ssistanceM, r. T. van Os for preparingt he figuresa ndMs. P.C. Assemsf or secretariaals sistanceT.h e work describedin this paper was supportedb y a grant from the Dutch CancerS ociety.",

year = "1996",

month = dec,

day = "16",

doi = "10.1016/S0925-4439(96)00060-9",

language = "English",

volume = "1317",

pages = "223--232",

journal = "Biochimica et Biophysica Acta - Molecular Basis of Disease",

issn = "0925-4439",

publisher = "Elsevier",

number = "3",

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Prins, JB, Langerak, AW, Dirks, RPH, Van Der Linden-Van Beurden, CAJ, De Laat, PAJM, Bloemers, HPJ & Versnel, MA 1996, 'Identification of regulatory sequences in the promoter of the PDGF B-chain gene in malignant mesothelioma cell lines', Biochimica et Biophysica Acta - Molecular Basis of Disease, vol. 1317, no. 3, pp. 223-232. https://doi.org/10.1016/S0925-4439(96)00060-9

TY - JOUR

T1 - Identification of regulatory sequences in the promoter of the PDGF B-chain gene in malignant mesothelioma cell lines

AU - Prins, Jan Bas

AU - Langerak, Anthonie W.

AU - Dirks, Ron P.H.

AU - Van Der Linden-Van Beurden, Carin A.J.

AU - De Laat, Petronella A.J.M.

AU - Bloemers, Henri P.J.

AU - Versnel, Marjan A.

N1 - Funding Information: We would like to thankp rof.dr. R. Bennera ndprof. dr. A. Hagemeijefro r continuoussu pportd, r. M. Verschuren for settingu p the EMSA technologyM, rs. E. Frankenf or technicala ssistanceM, r. T. van Os for preparingt he figuresa ndMs. P.C. Assemsf or secretariaals sistanceT.h e work describedin this paper was supportedb y a grant from the Dutch CancerS ociety.

PY - 1996/12/16

Y1 - 1996/12/16

N2 - Platelet-derived growth factor (PDGF) B-chain mRNA is readily detectable in malignant mesothelioma (MM) cell lines, but not in normal mesothelial (NM) cell lines. The high affinity receptor for PDGF B-chain dimers, the PDGF β-receptor, is expressed in MM cell lines. NM cell lines predominantly, express the PDGF α-receptor. Coexpression of the PDGF β-receptor and its ligand may lead to an autocrine growth stimulating loop in the malignant cell type. In nuclear run off experiments, PDGF B-chain mRNA was detectable in MM cells only, indicating an increased level of transcription in this cell type. The proximal promoter of the PDGF B-chain gene contains DNaseI hypersensitive (DH) sites and mediates reporter gene activation in both normal and malignant cells. Nuclear proteins, extracted from bath cell types, interact with DNA sequences within the proximal promoter around bp -64 to -61 relative to the transcription start site. Electrophoretic mobility shift assays (EMSAs) indicate that these factors are more abundantly present in the malignant than in the normal cell type. A DH site around -9.9 kb was found in both cell types. When tested in CAT assays, this region exerted a stimulatory effect on transcription in malignant cells. The elevated level of transcription of the PDGF B-chain gene in malignant cells may well be the result of interaction of regulatory sites in the proximal promoter and an enhancing element located at -9.9 kb from the transcription start site.

AB - Platelet-derived growth factor (PDGF) B-chain mRNA is readily detectable in malignant mesothelioma (MM) cell lines, but not in normal mesothelial (NM) cell lines. The high affinity receptor for PDGF B-chain dimers, the PDGF β-receptor, is expressed in MM cell lines. NM cell lines predominantly, express the PDGF α-receptor. Coexpression of the PDGF β-receptor and its ligand may lead to an autocrine growth stimulating loop in the malignant cell type. In nuclear run off experiments, PDGF B-chain mRNA was detectable in MM cells only, indicating an increased level of transcription in this cell type. The proximal promoter of the PDGF B-chain gene contains DNaseI hypersensitive (DH) sites and mediates reporter gene activation in both normal and malignant cells. Nuclear proteins, extracted from bath cell types, interact with DNA sequences within the proximal promoter around bp -64 to -61 relative to the transcription start site. Electrophoretic mobility shift assays (EMSAs) indicate that these factors are more abundantly present in the malignant than in the normal cell type. A DH site around -9.9 kb was found in both cell types. When tested in CAT assays, this region exerted a stimulatory effect on transcription in malignant cells. The elevated level of transcription of the PDGF B-chain gene in malignant cells may well be the result of interaction of regulatory sites in the proximal promoter and an enhancing element located at -9.9 kb from the transcription start site.

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U2 - 10.1016/S0925-4439(96)00060-9

DO - 10.1016/S0925-4439(96)00060-9

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JO - Biochimica et Biophysica Acta - Molecular Basis of Disease

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Identification of regulatory sequences in the promoter of the PDGF B-chain gene in malignant mesothelioma cell lines

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