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Nongenomic effects of estrogens on signal transduction pathways in estrogen-sensitive carcinoma cell lines
Breast Cancer Research volume 3, Article number: A22 (2001)
Research thus far has concentrated mainly on the classical steroid hormone (SH) receptors and on the underlying mechanisms of antihormone interactions with these receptors. This is mainly because, in the conventional view, estrogen (E) and progesterone produce most of their effects through interaction with cellular/nuclear receptors with subsequent alteration of the gene-regulating machinery. However, emerging data suggest that these lipophilic hormones are also able to produce rapid effects within several seconds, which cannot be adequately explained through the classical mechanism. Further investigation has recently led to the discovery of membrane-bound forms of E-receptors, which are coupled to cytosolic signal transduction proteins. These rapid responses have been observed in several tissues such as myometrial cells, neurons, endothelium, osteoblasts, granulosa cells and some breast cancer cell lines. The binding of E to these cell-surface forms of E-receptors is thought to activate several second messenger systems via the activation of G-proteins, resulting in the activation of different protein kinases. One such kinase is the mitogen-activated protein (MAP) kinase, which may serve as a stimulus for cell proliferation.
We report preliminary results showing the functional existence of such receptors in the human breast carcinoma cell line MCF-7. Using spectrofluorometry to measure the intracellular calcium concentration, evidence has been collected that the addition of E to these cells causes a rapid rise in the intracellular calcium concentration. This mechanism may prove to be an important initial signaling pathway, leading to the activation of specific protein kinases and subsequent proliferation.
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Djahansouzi, S., Niederacher, D., Hanstein, B. et al. Nongenomic effects of estrogens on signal transduction pathways in estrogen-sensitive carcinoma cell lines. Breast Cancer Res 3, A22 (2001). https://doi.org/10.1186/bcr347
- Granulosa Cell
- Carcinoma Cell Line
- Human Breast Carcinoma
- Intracellular Calcium Concentration
- Breast Carcinoma Cell Line