TY - JOUR
T1 - Hormonal carcinogenesis in breast cancer
T2 - cellular and molecular studies of malignant progression
AU - Clarke, Robert
AU - Skaar, Todd
AU - Baumann, Klaus
AU - Leonessa, Fabio
AU - James, Mattie
AU - Lippman, Jeremy
AU - Thompson, Erik W.
AU - Freter, Carl
AU - Brunner, Nils
PY - 1994/1
Y1 - 1994/1
N2 - We have established and characterized a series of variant cell lines in which to identify the critical factors associated with E2-induced malignant progression, and the acquisition to tamoxifen resistance in human breast cancer. Sublines of the hormone-dependent MCF-7 cell line (MCF7/MIII and MCF7/LCC1) form stable, invasive, estrogen independent tumors in the mammary fat pads of ovariectomized athymic nude mice. These cells retain expression of both estrogen (ER) and progesterone receptors (PGR), but retain sensitivity to each of the major structural classes of antiestrogens. The tamoxifen-resistant MCF7/LCC2 cells retain sensitivity to the inhibitory effects of the steroidal antiestrogen ICI 182780. By comparing the parental hormone-dependent and variant hormone-independent cells, we have demonstrated an altered expression of some estrogen regulated genes (PGR, pS2, cathepsin D) in the hormone-independent variants. Other genes remain normally estrogen regulated (ER, laminin receptor, EGF-receptor). These data strongly implicate the altered regulation of a specific subset or network of estrogen regulated genes in the malignant progression of human breast cancer. Some of the primary response genes in this network may exhibit dose-response and induction kinetics similar to pS2, which is constitutively upregulated in the MCF7/MIII, MCF7/LCC1 and MCF7/LCC2 cells.
AB - We have established and characterized a series of variant cell lines in which to identify the critical factors associated with E2-induced malignant progression, and the acquisition to tamoxifen resistance in human breast cancer. Sublines of the hormone-dependent MCF-7 cell line (MCF7/MIII and MCF7/LCC1) form stable, invasive, estrogen independent tumors in the mammary fat pads of ovariectomized athymic nude mice. These cells retain expression of both estrogen (ER) and progesterone receptors (PGR), but retain sensitivity to each of the major structural classes of antiestrogens. The tamoxifen-resistant MCF7/LCC2 cells retain sensitivity to the inhibitory effects of the steroidal antiestrogen ICI 182780. By comparing the parental hormone-dependent and variant hormone-independent cells, we have demonstrated an altered expression of some estrogen regulated genes (PGR, pS2, cathepsin D) in the hormone-independent variants. Other genes remain normally estrogen regulated (ER, laminin receptor, EGF-receptor). These data strongly implicate the altered regulation of a specific subset or network of estrogen regulated genes in the malignant progression of human breast cancer. Some of the primary response genes in this network may exhibit dose-response and induction kinetics similar to pS2, which is constitutively upregulated in the MCF7/MIII, MCF7/LCC1 and MCF7/LCC2 cells.
KW - breast cancer
KW - carcinogenesis
KW - estrogen
KW - hormone dependence
KW - malignant progression
UR - http://www.scopus.com/inward/record.url?scp=0027984448&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027984448&partnerID=8YFLogxK
U2 - 10.1007/BF00666157
DO - 10.1007/BF00666157
M3 - Article
C2 - 7881102
AN - SCOPUS:0027984448
SN - 0167-6806
VL - 31
SP - 237
EP - 248
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 2-3
ER -
