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Cytotoxic activities of a fusion protein comprised of TGFα and Pseudomonas exotoxin
Author(s) -
Siegall Clay B.,
Xu YongHua,
Chaudhary Vijay K.,
Adhya Sankar,
Fitzgerald David,
Pastan Ira
Publication year - 1989
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.3.14.2556314
Subject(s) - pseudomonas exotoxin , cytotoxic t cell , tgf alpha , biology , microbiology and biotechnology , fusion protein , exotoxin , receptor , cell culture , epidermal growth factor , cytotoxicity , biochemistry , gene , in vitro , genetics , toxin , recombinant dna
A cDNA encoding transforming growth factor type alpha (TGFα) was fused to the 5' end of a gene encoding a modified form of Pseudomonas exotoxin A (PE), which is devoid of the cell recognition domain (domain Ia). The chimeric molecule, termed TGFα‐PE40, was expressed in Escherichia coli and isolated from the periplasm or inclusion bodies depending on the construction expressed. TGFα‐PE40 was found to be extremely cytotoxic to cells displaying epidermal growth factor (EGF) receptors. Comparison with a similar molecule in which TGFa was placed at the carboxyl end of PE40 demonstrated the importance of the position of the cell recognition element; TGFα‐PE40 was found to be about 30‐fold more cytotoxic to cells bearing EGF receptors than PE40‐TGFα. In addition, TGFα‐PE40 was shown to be extremely cytotoxic to a variety of cancer cell lines including liver, ovarian, and colon cancer cell lines, indicating high levels of EGF receptor expression in these cells.—S iegall , C. B.; X u , Y.‐H.; C haudhary , V. K.; A dhya , S.; F itz G erald , D.; P astan , I. Cytotoxic activities of a fusion protein comprised of TGFα and Pseudomonas exotoxin. FASEB J. 3: 2647‐2652; 1989.