Membrane-initiated steroid action in breast and prostate cancer
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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2019, Frontiers in NeuroendocrinologyEstrogen receptor-alpha isoforms are the main estrogen receptors expressed in non-small cell lung carcinoma
2019, SteroidsCitation Excerpt :ERα is a dynamic protein, translocating within intracellular compartments. In addition to genomic transcriptional actions, the receptor triggers specific cytoplasmic/membrane signaling events and establishes cross-talk with other receptors (e.g. growth factor) [38]. Furthermore, ERα is submitted to several post-translational modifications, while proteasomal degradation may generate peptides with modulatory potential on transcription, cell fate and migration [39–42].
Estradiol receptor profile and estrogen responsiveness in laryngeal cancer and clinical outcomes
2019, SteroidsCitation Excerpt :An alternate hypothesis could be that the tumorigenic effects of E2 are the result of E2 binding to ERα46 or ERα66, has been shown previously in osteoblasts [47], or to an as-yet-uncharacterized novel membrane-bound estrogen receptor (Fig. 7). Classical sex hormone nuclear receptors have been found in the plasma membranes of hormone responsive cancers where they elicit rapid signaling pathways, which enhance cancer cell survival and proliferation [2]. From the plasma membrane it is thought that the classical receptors exert their effect through transactivation of the EGF or IGF-1 tyrosine kinase receptors in order to stimulate kinase cascades [38].
Can distinctly different rapid estrogen actions share a common mechanistic step?
2018, Hormones and BehaviorObesity and breast cancer – Role of estrogens and the molecular underpinnings of aromatase regulation in breast adipose tissue
2018, Molecular and Cellular EndocrinologyCitation Excerpt :This process leads to the regulation of transcription of estrogen-responsive genes that are important in various physiological and pathological processes, including carcinogenesis and tumor progression (Welboren et al., 2009). Besides these classical genomic effects, E2 can also elicit extra-nuclear or non-genomic actions related to the activation of rapid signaling pathways (Kampa et al., 2008). These extra-nuclear effects are mediated via a pool of ER present at the membrane or in the cytoplasm and lead to the rapid activation of downstream targets such as the mitogen-activated protein kinases (MAPK) pathway, which in turn modifies various cellular functions (Raffo et al., 2015).