TY - JOUR
T1 - EGF-related peptides are involved in the proliferation and survival of MDA-MB-468 human breast carcinoma cells
AU - De Luca, Antonella
AU - Casamassimi, Amelia
AU - Selvam, Mouna P.
AU - Losito, Simona
AU - Ciardiello, Fortunato
AU - Agrawal, Sudhir
AU - Salomon, David S.
AU - Normanno, Nicola
PY - 1999/2/4
Y1 - 1999/2/4
N2 - A majority of human breast carcinomas co-express the epidermal growth factor (EGF)-like peptides CRIPTO (CR), amphiregulin (AR) and transforming growth factor α (TGF-α). MDA-MB-468 breast carcinoma cells express CR, AR and TGFα, while SK-BR-3 cells express CR and TGF-α. Anti-sense phosphorothioate oligodeoxynucleotides (AS S-oligos) directed against either CR or TGF-α inhibit the proliferation of both cell lines. A 40-50% growth inhibition was observed at a 2-μM concentration of each AS S-oligo. Treatment with the AR AS S-oligo also resulted in a significant inhibition of MDA-MB-468 anchorage dependent growth (ADG). No significant growth inhibition was observed when MDA-MB-468 or SK-BR-3 cells were treated with a mis-sense S-oligo. The AS S-oligos inhibited the expression of AR, CR or TGF-α proteins and mRNAs, as assessed by immuno-cytochemistry and semi-quantitative RT-PCR. An additive growth-inhibitory effect was observed when MDA-MB-468 cells were treated with a combination of EGF-related AS S-oligos. Indeed, treatment of MDA-MB-468 cells with a combination of AR, CR and TGF-α AS S- oligos resulted in about 70% growth inhibition at a concentration of 0.7 μM each. Finally, treatment of MDA-MB-468 cells with a combination either of the 3 AS S-oligos or of an EGF receptor-blocking antibody (MAb 225) and either CR, AR or TGFα AS S-oligos resulted in a significant increase in DNA fragmentation. Our data suggest that the EGF-related peptides are involved in the proliferation and survival of breast carcinoma cells.
AB - A majority of human breast carcinomas co-express the epidermal growth factor (EGF)-like peptides CRIPTO (CR), amphiregulin (AR) and transforming growth factor α (TGF-α). MDA-MB-468 breast carcinoma cells express CR, AR and TGFα, while SK-BR-3 cells express CR and TGF-α. Anti-sense phosphorothioate oligodeoxynucleotides (AS S-oligos) directed against either CR or TGF-α inhibit the proliferation of both cell lines. A 40-50% growth inhibition was observed at a 2-μM concentration of each AS S-oligo. Treatment with the AR AS S-oligo also resulted in a significant inhibition of MDA-MB-468 anchorage dependent growth (ADG). No significant growth inhibition was observed when MDA-MB-468 or SK-BR-3 cells were treated with a mis-sense S-oligo. The AS S-oligos inhibited the expression of AR, CR or TGF-α proteins and mRNAs, as assessed by immuno-cytochemistry and semi-quantitative RT-PCR. An additive growth-inhibitory effect was observed when MDA-MB-468 cells were treated with a combination of EGF-related AS S-oligos. Indeed, treatment of MDA-MB-468 cells with a combination of AR, CR and TGF-α AS S- oligos resulted in about 70% growth inhibition at a concentration of 0.7 μM each. Finally, treatment of MDA-MB-468 cells with a combination either of the 3 AS S-oligos or of an EGF receptor-blocking antibody (MAb 225) and either CR, AR or TGFα AS S-oligos resulted in a significant increase in DNA fragmentation. Our data suggest that the EGF-related peptides are involved in the proliferation and survival of breast carcinoma cells.
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U2 - 10.1002/(SICI)1097-0215(19990209)80:4<589::AID-IJC17>3.0.CO;2-D
DO - 10.1002/(SICI)1097-0215(19990209)80:4<589::AID-IJC17>3.0.CO;2-D
M3 - Article
C2 - 9935161
AN - SCOPUS:0033521850
VL - 80
SP - 589
EP - 594
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 4
ER -