Elsevier

Steroids

Volume 73, Issues 9–10, October 2008, Pages 953-960
Steroids

Membrane-initiated steroid action in breast and prostate cancer

https://doi.org/10.1016/j.steroids.2007.12.009Get rights and content

Abstract

The mode of action of steroid hormones has been extended in recent years. In addition to their classical nuclear action (acting as transcription factors), they can also regulate cell-signaling phosphorylation cascades and exert actions that are initiated at the membrane and which, in most cases, are rapid. Even though research in this field was intensified during the last decade the nature of the up-stream receptor targets that mediates these rapid non-genomic actions remains to be better established. However, it became obvious that steroid signaling is not uniform, with a variety of modes of rapid action being described. There are several studies speculating a classical steroid receptor involvement in the rapid effects of steroids, localized at the cytoplasmic membrane and mediating effects directly or indirectly, via interactions with specific membrane structures (estrogen receptor (ER) isoforms have been shown to localize in caveolae) and/or other membrane receptors (like growth factor receptor). In addition, there are reports that suggest the existence of a distinct receptor, associated to the plasma membrane, being different from the classical, intracellular one. Non-genomic/extranuclear actions of steroids have been described in a number of different normal or cancer tissues independently of the presence of classical nuclear steroid receptors. In the present work, we review briefly the identification and signaling events of membrane-initiated steroid (androgen and estrogen) action in breast and prostate cancer cell lines and clinical specimens. Furthermore, we discuss the interaction of cytokine/growth factor receptors with membrane-acting steroids and their potential clinical implications.

Section snippets

Detection of membrane steroid binding sites in breast and prostate

Membrane steroid binding sites (receptors) have been identified in a number of cells of different origin. The main tool for this was the use of fluorescent or not steroids, conjugated to proteins, like BSA, that renders them impermeable to the cell membrane. Androgen sites were found in rat osteoblasts [1] and T cells, rat ventral prostate, rat epididymis [2], macrophages [3], [4], [5] and sertoli cells [6]. The existence of membrane androgen sites (mAR) was further identified on the cell

Membrane-initiated steroid actions and signaling

Steroid actions initiated at the membrane trigger many different intracellular-signaling pathways and affect crucial cellular functions such as cell proliferation, migration, secretion, and apoptosis.

Membrane steroid receptors and growth factors: it takes two to tango…

The interaction of steroid receptors with growth factor receptor signaling represents one of the emerging areas of elucidation of factors promoting progression and aggressiveness of human malignancies. The cross-link of steroid receptors with growth factors is not innovative as a knowledge. Nuclear steroid receptors act as sensors of growth factor-mediated signals. It is well known that in normal mammary gland PR isoforms cannot be induced by E2, unless EGF is present [62]. In the era of

Concluding remarks

To summarize, current knowledge on steroid structure and biology has revealed a complex interplay of these receptors with a number of essential signaling pathways. This intimate profile of expression and bidirectional regulation by growth factors provides further advantageous information on the mechanism of tumor progression and resistance to endocrine therapy. The challenging elucidation of these extraordinary gene signatures and their relevance in patient care implies a revolutionary catch up

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