Stimulation of cell proliferation and gene expression by binding to the estrogen receptor is one important mechanism in hormonal carcinogenesis; however, estrogenicity is not sufficient to explain the carcinogenic activity of all estrogens because some estrogens are not carcinogenic.
The differential expression pattern of estrogen receptor alpha (ER-alpha), estrogen receptor beta (ER-beta) and their co-activator/co-repressor proteins is thought to modulate estrogenic action and to be present already during the early stages of tumorigenesis.
Loss of expression of estrogen receptor (ER)-beta expression during prostate carcinogenesis and prevention of estrogen-mediated oxidative damage could be exploited in future PCa prevention strategies.
Cumulatively, our results suggest that Akt1 and ErbB2 are involved in in vivo tumorigenesis and modulation of estrogen receptor-alpha expression and activity.
Data support that (1) normal human peripheral blood cells (mononuclear cells, total lymphocytes, T as well as B lymphocytes, and NK cells) express both estrogen receptor subtypes (ERα and ERβ), (2) B-cell malignancies express mainly ERβ while selective ERβ agonists inhibit cell growth and induce apoptosis, (3) estrogens regulate, via an ER-mediated pathway, gene expression of cyclins, kinases, bcl-2 proto-oncogene, activation-induced deaminase (AID), and transcription factors, associated with changes in BCR signaling and B cell tumorigenesis.
In hormone-dependent tissues such as breast and ovary, tumorigenesis is associated with an altered expression ratio between the two estrogen receptor (ER) subtypes.
These data show that ERbeta is the predominant ER subtype in the human colon and that decreased levels of ERbeta1 and ERbeta2 mRNA are associated with colonic tumorigenesis in females.
Given that prolonged exposure to unopposed estrogen has been implicated in endometrial carcinogenesis, our goal was to evaluate the effect of As(2)O(3) on regulation of estrogen receptor-alpha (ERa) expression in endometrial cancer cells.
Our results thus demonstrated that PEITC functions as a more potent ER-alpha'disruptor' than the well-known ICI 182,780 to abrogate ER-mediated mitogenic oestrogen signaling in breast cancer cells, which provides a molecular explanation for the strong growth inhibitory activity of ITCs in breast cancer cells, and a rational for further exploration of ITCs as chemopreventive agents for human mammary carcinogenesis.
The relative level of expression of some estrogen receptor variant mRNAs and possibly progesterone receptor variant mRNAs is altered during breast tumorigenesis and breast cancer progression.
In response to the elevated levels of E, the ERα signaling was accentuated in the ovarian epithelial cells of ERαd/d mice, triggering increased ERα-dependent gene expression, abnormal cell proliferation, and tumorigenesis.
Application of PSEA to the expression data in this study revealed not only well-known ER-dependent and cellular morphology-dependent protein abundance changes, but also significant alterations of downstream targets for multiple transcription factors (TFs), suggesting a role for specific gene regulatory pathways in breast tumorigenesis.
Given that prolonged exposure to unopposed estrogen is associated with endometrial cancer development and that the promoter region of the catalytic subunit of the telomerase enzyme, hTERT, contains putative estrogen response elements (EREs), we postulated that estrogen-receptor (ER)-mediated induction of telomerase activity may play an important role in endometrial carcinogenesis.
Estrogen receptor (ER) coregulator overexpression promotes carcinogenesis and/or progression of endocrine related-cancers in which steroid hormones are powerful mitogenic agents.