Down-regulation of HER-2 expression in human breast cancer cell HBC-4 and ZR75-1 by nitrogen-mustard-N-oxide.
OBJECTIVE
The human epidermal growth factor receptor type 2 (HER-2) seems to be sensitive to nitrogen mustard, because nitrogen mustard heavily alkylates on guanine. In this study, we examined the effects of nitrogen mustard on cell growth and expression of HER-2 proteins in cultured human breast cancer cells.


METHODS
The HER-2 protein levels on the cell surface of breast cancer cells were evaluated following treatment with various concentrations of Nitrogen-mustard-N-oxide using flow cytometry.


RESULTS
The HER-2 proteins were detected as high and moderate in ZR75-1 and HBC-4, respectively. The addition of 0.5, 1 and 3 mg/ml of Nitrogen-mustard-N-oxide to the medium significantly decreased in the HER-2 protein with a sharp peak in both the ZR75-1 and HBC-4 cells. The mean value of the HER-2 protein expression in HBC-4 cells was 60%, 51% and 34% of the control, with the growth of 80%, 70% and 50% of the control at 72 hours, respectively. The mean value of HER-2 protein in ZR75-1 cells was 94%, 93% and 70% of the control, with the growth of 70%, 50% and 30% of the control at 72 hours, respectively. A lower dose of Nitrogen-mustard-N-oxide insufficient for growth inhibition did not show a decrease. Only the addition of Nitrogen-mustard-N-oxide in a sufficiently high dose to show growth inhibition down-regulated the HER-2 protein expression in human breast cancer cells.


CONCLUSIONS
We concluded that high concentrations of cyclophosphamide(CPA) might be able to inhibit cell growth through down-regulation of HER-2 protein level in breast cancer cell lines.
Sai
Syuuitu
S
Department of Gastroenterological Surgery Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku Kobe, Japan.
Furuya
Yoshihiko
Y
Fujino
Yasuhiro
Y
Kuroda
Yoshikazu
Y
D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D008466:Mechlorethamine / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics*
D018906:Antineoplastic Agents, Alkylating; D006131:Growth Inhibitors; D008466:Mechlorethamine; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human