Cytotoxic effects of TGF-α-Pseudomonas exotoxin A fusion protein in human pancreatic carcinoma cells

Rae Lynn Baldwin, Michael S. Kobrin, Trang Tran, Ira Pastan, Murray Korc

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The epidermal growth factor (EGF) receptor is overexpressed in human pancreatic cancers and cultured cell lines. TP40 is a chimeric protein composed of transforming growth factor-α (TGF-α) linked to a modified Pseudomonas exotoxin A (PE40) that exerts growth inhibitory effects on cells bearing a high number of EGF receptors. Therefore, we compared the effect of TP40 on the growth of Chinese hamster ovary (CHO) cells expressing varying levels of the EGF receptor and on the growth of two human pancreatic cancer cell lines. The growth of CHO cells devoid of endogenous EGF receptors was minimally altered by high concentrations of TP40, even following a 72-h incubation period. In contrast, in CHO cells expressing ~95,000 and 438,000 EGF receptors per cell, one-half maximal growth inhibition occurred at 5 and 3 ng/ml TP40, respectively. Following a 72-h incubation in T3M4 and COLO 357 human pancreatic cancer cells, one-half maximal growth inhibition occurred at 0.2 and 0.4 ng/ml TP40, respectively. This effect was significantly greater than that of native Pseudomonas exotoxin A. These findings indicate that human pancreatic cancer cells are markedly sensitive to the growth inhibitory effects of TP40 and raise the possibility that TP40 may have a therapeutic role in this disorder.

Original languageEnglish (US)
Pages (from-to)16-21
Number of pages6
JournalPancreas
Volume13
Issue number1
StatePublished - 1996
Externally publishedYes

Fingerprint

Transforming Growth Factors
Pancreatic Neoplasms
Growth
Cricetulus
Proteins
Ovary
Epidermal Growth Factor Receptor
Cell Line
Pancreatic Carcinoma
transforming growth factor alpha-Pseudomonas exotoxin A (40)
Pseudomonas aeruginosa toxA protein
Cultured Cells
ErbB Receptors

Keywords

  • Epidermal growth factor receptor
  • Growth inhibition
  • TP40

ASJC Scopus subject areas

  • Gastroenterology
  • Endocrinology

Cite this

Baldwin, R. L., Kobrin, M. S., Tran, T., Pastan, I., & Korc, M. (1996). Cytotoxic effects of TGF-α-Pseudomonas exotoxin A fusion protein in human pancreatic carcinoma cells. Pancreas, 13(1), 16-21.

Cytotoxic effects of TGF-α-Pseudomonas exotoxin A fusion protein in human pancreatic carcinoma cells. / Baldwin, Rae Lynn; Kobrin, Michael S.; Tran, Trang; Pastan, Ira; Korc, Murray.

In: Pancreas, Vol. 13, No. 1, 1996, p. 16-21.

Research output: Contribution to journalArticle

Baldwin, RL, Kobrin, MS, Tran, T, Pastan, I & Korc, M 1996, 'Cytotoxic effects of TGF-α-Pseudomonas exotoxin A fusion protein in human pancreatic carcinoma cells', Pancreas, vol. 13, no. 1, pp. 16-21.
Baldwin, Rae Lynn ; Kobrin, Michael S. ; Tran, Trang ; Pastan, Ira ; Korc, Murray. / Cytotoxic effects of TGF-α-Pseudomonas exotoxin A fusion protein in human pancreatic carcinoma cells. In: Pancreas. 1996 ; Vol. 13, No. 1. pp. 16-21.
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