Suppression of ovarian cancer cell tumorigenicity and evasion of cisplatin resistance using a truncated epidermal growth factor receptor in a rat model

John K. Chan, Huyen Pham, Juan You Xue, Noelle G. Cloven, Robert A. Burger, G. Scott Rose, Kristi Van Nostrand, Murray Korc, Philip J. DiSaia, Hung Fan

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The overexpression of the epidermal growth factor receptor (EGFR) is associated with a poor prognosis in ovarian cancer. The dominant-negative EGFR (EGFR-DNR) is a truncated receptor that lacks the tyrosine kinase domain and is devoid of signaling capability. This study tested the effects of a EGFR-DNR approach in ovarian cancer cells. NuTu-19, a rat ovarian cancer cell line was rendered resistant to cisplatin. Both NuTu-19 and resistant cells were infected with a retroviral vector containing the EGFR-DNR. NuTu-19 and NuTu-DNR (NuTu-19 cells expressing the EGFR-DNR) were injected into Fisher 344 immunocompetent rats. Western blot analyses were used to assess signal transduction pathways. All rats injected with NuTu-DNR cells remained healthy following tumor injection. In contrast, 100% of the rats injected with the NuTu-19 and NuTu-Sham (NuTu-19 cells expressing an empty vector) died of disease progression at the end of 15 weeks (P = 0.00009). On Western blot analysis, both NuTu-19 and NuTu-Sham cells showed a strong activation of mitogen-activated protein kinase (MAPK) after exposure to EGF. Cisplatin-resistant cell lines showed an enhanced EGF stimulatory effect via the MAPK pathway compared with parental cells. The EGFR-DNR significantly reduced the ability of EGF to induce cell signaling through the MAPK pathway. Lastly, the EGFR-DNR can partially reverse cisplatin resistance in drug-resistant cells. The EGFR-DNR approach suggests that EGFR confers a growth advantage to NuTu-19 cells in vivo. Thus, EGFR blockade may ultimately prove to be a useful therapeutic tool in the treatment of cisplatin-sensitive and cisplatin-resistant ovarian cancers.

Original languageEnglish (US)
Pages (from-to)3243-3248
Number of pages6
JournalCancer Research
Volume65
Issue number8
StatePublished - Apr 15 2005
Externally publishedYes

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Epidermal Growth Factor Receptor
Ovarian Neoplasms
Cisplatin
Mitogen-Activated Protein Kinases
Epidermal Growth Factor
Western Blotting
Cell Line
Receptor Protein-Tyrosine Kinases
Drug Resistance
Disease Progression
Signal Transduction
Injections

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Chan, J. K., Pham, H., Xue, J. Y., Cloven, N. G., Burger, R. A., Rose, G. S., ... Fan, H. (2005). Suppression of ovarian cancer cell tumorigenicity and evasion of cisplatin resistance using a truncated epidermal growth factor receptor in a rat model. Cancer Research, 65(8), 3243-3248.

Suppression of ovarian cancer cell tumorigenicity and evasion of cisplatin resistance using a truncated epidermal growth factor receptor in a rat model. / Chan, John K.; Pham, Huyen; Xue, Juan You; Cloven, Noelle G.; Burger, Robert A.; Rose, G. Scott; Van Nostrand, Kristi; Korc, Murray; DiSaia, Philip J.; Fan, Hung.

In: Cancer Research, Vol. 65, No. 8, 15.04.2005, p. 3243-3248.

Research output: Contribution to journalArticle

Chan, JK, Pham, H, Xue, JY, Cloven, NG, Burger, RA, Rose, GS, Van Nostrand, K, Korc, M, DiSaia, PJ & Fan, H 2005, 'Suppression of ovarian cancer cell tumorigenicity and evasion of cisplatin resistance using a truncated epidermal growth factor receptor in a rat model', Cancer Research, vol. 65, no. 8, pp. 3243-3248.
Chan, John K. ; Pham, Huyen ; Xue, Juan You ; Cloven, Noelle G. ; Burger, Robert A. ; Rose, G. Scott ; Van Nostrand, Kristi ; Korc, Murray ; DiSaia, Philip J. ; Fan, Hung. / Suppression of ovarian cancer cell tumorigenicity and evasion of cisplatin resistance using a truncated epidermal growth factor receptor in a rat model. In: Cancer Research. 2005 ; Vol. 65, No. 8. pp. 3243-3248.
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