Decrease in the level and mRNA expression of LH-RH and EGF receptors after treatment with LH-RH antagonist Cetrorelix in DU-145 prostate tumor xenografts in nude mice

Najib Lamharzi, Gábor Halmos, Andreas Jungwirth, Andrew V Schally

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Using radioligand binding, RT-PCR, and Southern blot analyses, we evaluated whether agonist [D-Trp6]LH-RH and antagonist Cetrorelix could affect the levels of receptors for LH-RH and EGF and expression of mRNA for these receptors in DU-145 human androgen-independent prostate cancers xenografted into nude mice. Radioligand binding studies showed the presence of specific high affinity receptors for LH-RH and EGF in DU-145 prostate tumors. Cetrorelix, but not [D-Trp6]LH-RH significantly inhibited tumor growth. The concentration of LH-RH receptors was reduced by 22% (p<0.05) and 67% (p<0.01) after 4 weeks of treatment with [D-Trp6]LH-RH and Cetrorelix respectively. The concentration of EGF receptors fell by 48% (p<0.05) in the [D-Trp6]LH-RH group, whereas Cetrorelix led to a 66% reduction (p<0.01). The expression of LH-RH and EGF receptor mRNA was investigated by RT-PCR analysis followed by Southern blotting. Densitometric analysis of the developed bands showed that the antagonist Cetrorelix decreased the expression of LH-RH receptor mRNA by 55% (p<0.01) compared to control group while the 20% reduction after treatment with the LH-RH agonist was non-significant. Treatment with [D-Trp6]LH-RH and Cetrorelix also reduced the expression of EGF receptor mRNA by 35% and 68% respectively (both, p<0.01) compared to control group. In conclusion, these data demonstrate that growth inhibition of DU-145 prostate tumors induced by prolonged administration of LH-RH antagonist Cetrorelix is accompanied by a marked decrease in the concentration of LH-RH and EGF receptors as well as in their mRNA levels.

Original languageEnglish
Pages (from-to)429-435
Number of pages7
JournalInternational Journal of Oncology
Volume13
Issue number3
StatePublished - Sep 1 1998
Externally publishedYes

Fingerprint

Heterografts
Nude Mice
Gonadotropin-Releasing Hormone
Prostate
Messenger RNA
Neoplasms
LH Receptors
Southern Blotting
Epidermal Growth Factor Receptor
Epidermal Growth Factor
cetrorelix
ErbB Receptors
Polymerase Chain Reaction
Control Groups
Growth
Androgens
Prostatic Neoplasms

Keywords

  • Androgen-independent prostate cancer
  • LH-RH antagonist
  • RT-PCR
  • Southern blotting

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Decrease in the level and mRNA expression of LH-RH and EGF receptors after treatment with LH-RH antagonist Cetrorelix in DU-145 prostate tumor xenografts in nude mice. / Lamharzi, Najib; Halmos, Gábor; Jungwirth, Andreas; Schally, Andrew V.

In: International Journal of Oncology, Vol. 13, No. 3, 01.09.1998, p. 429-435.

Research output: Contribution to journalArticle

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title = "Decrease in the level and mRNA expression of LH-RH and EGF receptors after treatment with LH-RH antagonist Cetrorelix in DU-145 prostate tumor xenografts in nude mice",
abstract = "Using radioligand binding, RT-PCR, and Southern blot analyses, we evaluated whether agonist [D-Trp6]LH-RH and antagonist Cetrorelix could affect the levels of receptors for LH-RH and EGF and expression of mRNA for these receptors in DU-145 human androgen-independent prostate cancers xenografted into nude mice. Radioligand binding studies showed the presence of specific high affinity receptors for LH-RH and EGF in DU-145 prostate tumors. Cetrorelix, but not [D-Trp6]LH-RH significantly inhibited tumor growth. The concentration of LH-RH receptors was reduced by 22{\%} (p<0.05) and 67{\%} (p<0.01) after 4 weeks of treatment with [D-Trp6]LH-RH and Cetrorelix respectively. The concentration of EGF receptors fell by 48{\%} (p<0.05) in the [D-Trp6]LH-RH group, whereas Cetrorelix led to a 66{\%} reduction (p<0.01). The expression of LH-RH and EGF receptor mRNA was investigated by RT-PCR analysis followed by Southern blotting. Densitometric analysis of the developed bands showed that the antagonist Cetrorelix decreased the expression of LH-RH receptor mRNA by 55{\%} (p<0.01) compared to control group while the 20{\%} reduction after treatment with the LH-RH agonist was non-significant. Treatment with [D-Trp6]LH-RH and Cetrorelix also reduced the expression of EGF receptor mRNA by 35{\%} and 68{\%} respectively (both, p<0.01) compared to control group. In conclusion, these data demonstrate that growth inhibition of DU-145 prostate tumors induced by prolonged administration of LH-RH antagonist Cetrorelix is accompanied by a marked decrease in the concentration of LH-RH and EGF receptors as well as in their mRNA levels.",
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