Group items tagged

Progesterone metabolites play key role in breast cancer carcinogenesis or inhibition of carcinogenesis.  The key active progesterone metabolites discussed in this article are 5 alpha pregnene and 3 alpha hydroxyprogesterone.

Testosterone, metabolites and prostate carcinogenesis.

Acute inflammation is a response to an alteration induced by a pathogen or a physical or chemical insult, which functions to eliminate the source of the damage and restore homeostasis to the affected tissue. However, chronic inflammation triggers cellular events that can promote malignant transformation of cells and carcinogenesis. Several inflammatory mediators, such as TNF-α, IL-6, TGF-β, and IL-10, have been shown to participate in both the initiation and progression of cancer. In this review, we explore the role of these cytokines in important events of carcinogenesis, such as their capacity to generate reactive oxygen and nitrogen species, their potential mutagenic effect, and their involvement in mechanisms for epithelial mesenchymal transition, angiogenesis, and metastasis. Finally, we will provide an in-depth analysis of the participation of these cytokines in two types of cancer attributable to chronic inflammatory disease: colitis-associated colorectal cancer and cholangiocarcinoma.

In this animal study, estradiol is added to Testosterone to increase prostate carcinogenesis.  Previous rat studies have shown that adding estradiol to Testosterone, which occurs naturally, increases prostate cancer risk.  

review article points to the concept that it is not Testosterone, but Estrogen that is involved with carcinogenesis of the prostate.

loss of ER-beta expression is associated with increased carcinogenesis, suggesting a protective role for ER-beta against tumor proliferation.

This study finds a strong correlation between advancing breast cancer, decreased catalase and SOD with increasing MDA.  The authors of this study conclude this is a key factor in carcinogenesis and not a by-product of cancer.  This flies in the face of traditional medicines fear of antioxidant therapy in cancer.

Telomerase activity and longer telomere length is shown to correlated inversely with many chronic diseases of aging.  In contrast, telomerase activity is found to be involved in carcinogenesis.  Increased carcinogenic potential of telomerase activity has not borne out in studies.  In addition, increased CD8 cell activity as a result of telomerase activation will actually decrease carcinogenic potential via NK activation.

Adding Estradiol to Testosterone in rate model significantly increases prostate carcinogenesis in rat model.

Bisphenol A exposure in utero found to increase prostate cancer risk later in life.  This exposure occurred at typical life exposure levels as found in umbilical cord blood sampling,  This occurred through stem cell self-renewal and progenitor amplification

hypermethylation and hypomethylation shown to play roles in carcinogenesis.

hypomethylation and carcinogenesis.

hyper and hypo methylation known to be associated with carcinogenesis.  One carcinogenic potential of hypermethylation is through suppression of tumor suppression genes.

Great discussion of how 5alpha-androstane-3beta, 17beta-androstanediol interacts with ER beta as an estrogen to inhibit proliferation of the prostate and carcinogenesis.

Methylation of the ER beta gene promoter region decreases ER beta expression and this has been associated with carcinogenesis of the prostate.

Loss of ER beta expression is a very important step in carcinogenesis in hormone responsive cancers.  This includes breast cancer in women and prostate cancer in men, but this also includes colorectal cancer in both.

ER beta expression that is lost in prostate carcinogenesis occurs via methylation at the ER beta gene promoter sites 19CpG.  What is really interesting is that ER beta expression was present in all of the samples with BPH, but was absent in 83% of the prostate cancer samples.

aromatase knockout mice, thus elevated androgens without estrogen production, develop BPH but not prostate cancer.  This points to estrogen as the important hormone in carcinogenesis of the prostate. Granted this is a animal model.

Study finds that ER beta inhibits invasion, proliferation and actually triggers cell death of prostate cancer cells.  This fits with the other data that loss of ER beta promotes carcinogenesis.

Estrogen plays a critical role in the initiation of carcinogenesis of prostate cancer through the ER alpha/beta expression.  As the authors state in their conclusion, "...ER alpha signaling potentiates the carcinogenic effects of androgens on the prostatic epithelium."