17 beta-estradiol regulates and v-Ha-ras transfection constitutively enhances MCF7 breast cancer cell interactions with basement membrane.

Abstract

The interaction of a line of human breast carcinoma cells (MCF7) with basement membrane components, particularly laminin, was altered by exposure of the cells to estrogen as well as by transfection of the cells with the v-Ha-ras oncogene. In both cases, the cells show a greater ability to attach to a laminin substrate, to migrate to laminin, to grow in the presence of a basement membrane matrix, and to cross barriers of reconstituted basement membrane. These responses were associated with an increase in the expression of laminin receptors. It is postulated that the increase in the invasive behavior of the cells treated with estrogen or transfected with v-Ha-ras is related to the increased number of laminin receptors and their interaction with laminin. Estrogen had no discernible effect on the v-Ha-ras transfected cells. It appears that in the MCF7 cells, the malignant phenotype is under hormonal control and that this control is bypassed after v-Ha-ras transfection.Transfection of MCF7 cells with the v-Ha-ras oncogene bypasses the estrogen requirement for tumorigenicity (26).To better characterize mechanisms involved in the metastatic process, we have studied the interactions of MCF7 breast cancer cells in vitro with a reconstituted basement membrane or with laminin alone in the presence of estradiol and after v-Ha-ras transfection. The matrigel, or reconstituted basement membrane, has typical basement membrane components, but these are probably not in the proportions present in these structures in situ. We find that estrogen increases the adhesion, migration, chemoinvasion, and growth of these cells in the presence of laminin or of reconstituted basement membrane. Cells transfected with v-Ha-ras oncogene express these same activities constitutively and are unaffected by estrogen. Both estrogen and v-Ha-ras transfection confer an enhanced number of laminin receptors on these cells.

Estrogens and their receptors in breast cancer progression: a dual role in cancer proliferation and invasion

“…The initial studies indicated that the invasiveness of MCF7 breast cancer cells was increased by antiestrogens [81,82]. More recent studies have demonstrated that estradiol significantly reduces invasiveness and that this inhibition is reversed by antiestrogens [83][84][85][86][87].…”

An Inherent Role of Integrin-Linked Kinase-Estrogen Receptor α Interaction in Cell Migration

“…Recently, the nongenomic effects of estrogen have been linked to endothelial monolayer permeability and migration, as well as endometrial cancer cell migration (15)(16)(17). However, despite the fact that E2 signaling could affect breast cancer cell adhesion and migration (18), the contribution of ILK signaling node in rapid estrogen responses and in breast cancer cell migration remains unknown. In this context, it is interesting to note that ERa and ILK have been shown to regulate overlapping physiologic processes and to share common interacting partners (i.e., heat shock protein 90 and caveolin-1; refs.…”

C-7 Progesterone Analogues and MDR1 in Breast Cancer

“…227 -228 In NIH/3T3 cells, transfection with either v-Haras or genomic DNA containing various forms of activated ras also resulted in increased invasiveness across the amniotic membrane in vitro and metastatic dissemination in vivo. 229 MCF-7 cells transfected with v-Ha-ra.y show increased in vitro invasiveness of Matrigel, increased migration potential, and increased recognition of laminin, 230 but no apparent increases in metastatic potential in nude mice. 2 -11 -232 Although both of the 184 sublines (A1N4 and B5) are transformed to a tumorigenic phenotype by expression of ras alone, only the initially more invasive AlN4 cells respond to ras transformation with increased invasiveness.…”