LCC9 Abstract

acquired resistance to anti-estrogen is a major problem in the clinical treatment of endocrine reaction initially metastatic breast cancer. We have already shown that estrogen and MCF7 independent -responsive / LCC1 human breast cancer cells to resist triphenylethylene selected tamoxifen, a variant (MCF7 / LCC2) produce, sensitivity steroidal antiestrogen ICI 182,780 (N. Brunner et al reserves., Cancer Res, 53 :. 3229-3232, 1993). We now have the progressive vitro selection from 10:00 to 1 microM ICI 182,780 against MCF7 / LCC1 and gets a variant ICI 182,780 permanent resistant MCF7 / designated LCC9 applied. Unlike MCF7 / MCF7 4-hydroxy-LCC2 selected cells / LCC9 to present a complete cross-resistance to tamoxifen, has been exposed, despite never to this drug. Tamoxifen cross resistance born at the beginning of the selection, the following selection against only 0.1 nM ICI 182,780 clear. Although limited resistance against ICI 182,780 182,780 also observed resistance was not recognized until the selection pressure to 100 nM ICI increased 182,780 full HERE. Cross-resistance to tamoxifen remained during this additional selection. Despite their cross antiestrogen resistance, the MCF7 / LCC9 a level of expression of estrogen receptor retain comparable to that of their parent cells / LCC1 of MCF7. Whereas cells / LCC1 of MCF7 retain estrogen-inducible expression of progesterone receptors, show MCF7 / LCC9 of expression upregulated in both the progesterone receptor mRNA and protein unresponsive estrogen. independent estrogen and -responsive components MCF7 / LCC9 phenotype are obviously in vivo. These cells slowly form tumors in nude athymic mice ovariectomized but develop mitogenic response of estrogen supplements. The in vivo growth of MCF7 tumors / of LCC9 not affected by treatment with ICI 182,780. Although there is evidence of tamoxifen stimulation of tumor growth, this did not reach statistical significance. If this cross-resistance pattern occurs in some patients with breast cancer, antiestrogens triphenylethylene as first-line treatment with a cross-over administration of compounds to a repeat steroid may be advantageous.