Estrogen and its receptors in cancer

Abstract

The involvement of estrogen and its receptors in the development of cancer has been known for years. However, the exact mechanism responsible is far from clear. The estrogen-mediated carcinogenic process is complicated by recent findings, which reveal that estrogens have multiple functions in cells, which can be either adverse or beneficial, and that the effects of estrogen may be cell-type or organ dependent. The estrogenic effect may be also greatly influenced by the state of two estrogen receptors, ERalpha and ERbeta. This review will discuss the role and function of estrogens and its receptors in cancers of three categories: (1) Breast cancer and gynecologic cancers, (2) Cancers of endocrine organs, (3) Lung cancer and cancers of digestive system. We will also review some novel treatments aiming to interfere with relevant pathways mediated by estrogens and its receptors.

GPCRs and cancer

“…Estrogens influence many physiological processes, but are also implicated in the development or progression of various types of cancer [134] . The multiple biological actions elicited by these hormones have traditionally been attributed to the classical nuclear estrogen receptor (ER)α and ERβ, which act as ligand-activated transcription factors [134] .…”

“…The multiple biological actions elicited by these hormones have traditionally been attributed to the classical nuclear estrogen receptor (ER)α and ERβ, which act as ligand-activated transcription factors [134] . Surprisingly, a member of the GPCR family, GPR30/GPER, was recently shown to mediate the multifaceted actions of estrogens in different tissues including cancer cells [135] .…”

Conjugation of a Ru(II) Arene Complex to Neomycin or to Guanidinoneomycin Leads to Compounds with Differential Cytotoxicities and Accumulation between Cancer and Normal Cells

“…[15][16] Among such modifications, derivatization of non-leaving ligands with a carrier molecule has tremendous potential to generate selective, less toxic metallodrugs. The potential of this targeted strategy is particularly promising when metal complexes, either organometallic or classical coordination compounds, are attached to biomolecules [17][18][19][20][21][22][23][24] whose receptors are overexpressed on the membrane of tumoral cells [25][26][27][28] or to organic molecules with high affinity with a given biological target (proteins or nucleic acids). 29 Such differences in cytotoxic activity for each compound in a particular cell line, either normal or tumoral, could be interpreted in terms of cell uptake and accumulation efficiency.…”

“…[17][18][19][20][21][22][23][24] This targeted strategy has a tremendous potential in the development of more efficient, less toxic, selective metallodrugs in chemotherapy because receptors for these carrier molecules are over-expressed in the membrane of tumoral cells. [25][26][27][28] Another strategy to improve efficiency of a metal-based drug is to increase its affinity with its ultimate biological target. This strategy has been explored mainly with platinum complexes through the covalent attachment to compounds with high affinity for DNA (minor groove binders or intercalators) or to synthetic oligonucleotides or Peptide Nucleic Acids complementary to specific DNA sequences.…”

Gender and Age Related Modulation of Xenoestrogen-Induced Tumorigenesis

“…Current data show that all cancer types are in some way related with the level of estrogen, estrogen receptors and aromatase or their polymorphisms [11][12][13][14]. Generally estrogen receptor (ER) alpha promotes proliferation, while ER beta supresses it but this is not the rule for all tissues; moreover, the ER status varies between neoplastic tissues.…”