TY - JOUR
T1 - Inhibitory effect of the peptide epitalon on the development of spontaneous mammary tumors in HER-2/neu transgenic mice
AU - Anisimov, Vladimir N.
AU - Khavinson, Vladimir K H
AU - Provinciali, Mauro
AU - Alimova, Irina N.
AU - Baturin, Dmitri A.
AU - Popovich, Irina G.
AU - Zabezhinski, Mark A.
AU - Imyanitov, Eugeni N.
AU - Mancini, Romina
AU - Franceschi, Claudio
PY - 2002/9/1
Y1 - 2002/9/1
N2 - Female FVB/N HER-2/neu transgenic mice from the age of 2 months were subcutaneously injected with saline, the peptide Epitalon® (Ala-Glu-Asp-Gly) or with the peptide Vilon® (Lys-Glu) in a single dose of 1 μg/mouse for 5 consecutive days every month. Epitalon treatment reduced the cumulative number and the maximum size of tumors (p <0.05). Furthermore, the number of mice bearing 1 mammary tumor was increased, whereas the number of mice bearing 2 or more mammary tumors was reduced in Epitalon-treated in comparison to saline-treated animals (p <0.05). The size but not the number of lung metastases was reduced in Epitalon- treated compared to saline-treated mice (p <0.05). The treatment with Vilon produced significant negative effects when compared to the control group, with an increased incidence of mammary cancer development (p <0.05), a shorter mean latent period of tumors (p <0.05) and an increased cumulative number of tumors (p <0.05). A 3.7-fold reduction in the expression of HER-2/neu mRNA was found in mammary tumors from HER-2/neu transgenic mice treated with Epitalon compared to control animals. The expression of mRNA for HER-2/neu was also partially reduced in Vilon-treated mice, but it remained significantly higher in Vilon- than in Epitalon-treated animals (1.9-fold increase). The data demonstrate the inhibitory effect of Epitalon in the development of spontaneous mammary tumors in HER-2/neu mice, suggesting that a downregulation of HER-2/neu gene expression in mammary adenocarcinoma may be responsible, at least in part, for the antitumor effect of the peptide.
AB - Female FVB/N HER-2/neu transgenic mice from the age of 2 months were subcutaneously injected with saline, the peptide Epitalon® (Ala-Glu-Asp-Gly) or with the peptide Vilon® (Lys-Glu) in a single dose of 1 μg/mouse for 5 consecutive days every month. Epitalon treatment reduced the cumulative number and the maximum size of tumors (p <0.05). Furthermore, the number of mice bearing 1 mammary tumor was increased, whereas the number of mice bearing 2 or more mammary tumors was reduced in Epitalon-treated in comparison to saline-treated animals (p <0.05). The size but not the number of lung metastases was reduced in Epitalon- treated compared to saline-treated mice (p <0.05). The treatment with Vilon produced significant negative effects when compared to the control group, with an increased incidence of mammary cancer development (p <0.05), a shorter mean latent period of tumors (p <0.05) and an increased cumulative number of tumors (p <0.05). A 3.7-fold reduction in the expression of HER-2/neu mRNA was found in mammary tumors from HER-2/neu transgenic mice treated with Epitalon compared to control animals. The expression of mRNA for HER-2/neu was also partially reduced in Vilon-treated mice, but it remained significantly higher in Vilon- than in Epitalon-treated animals (1.9-fold increase). The data demonstrate the inhibitory effect of Epitalon in the development of spontaneous mammary tumors in HER-2/neu mice, suggesting that a downregulation of HER-2/neu gene expression in mammary adenocarcinoma may be responsible, at least in part, for the antitumor effect of the peptide.
KW - HER-2/neu
KW - Mammary cancer
KW - Peptide
KW - Transgenic mice
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U2 - 10.1002/ijc.10570
DO - 10.1002/ijc.10570
M3 - Article
C2 - 12209581
AN - SCOPUS:0036722946
VL - 101
SP - 7
EP - 10
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 1
ER -