Abstract
Sex steroid hormones, estrogen, progesterone and androgen, play pivotal roles in sex differentiation and development, and in reproductive functions and sexual behavior. Studies have shown that sex steroid hormones are the key regulators in the development and progression of endocrine-related cancers, especially the cancers of the reproductive tissues. The actions of estrogen, progesterone and androgen are mediated through their cognate intracellular receptor proteins, the estrogen receptors (ER), the progesterone receptors (PR) and the androgen receptor (AR), respectively. These receptors are members of the nuclear receptor (NR) superfamily, which function as transcription factors that regulate their target gene expression. Proper functioning of these steroid receptors maintains the normal responsiveness of the target tissues to the stimulations of the steroid hormones. This permits the normal development and function of reproductive tissues. It can be inferred that factors influencing the expression or function of steroid receptors will interfere with the normal development and function of the target tissues, and may induce pathological conditions, including cancers. In addition to the direct contact with the basal transcription machinery, nuclear receptors enhance or suppress transcription by recruiting an array of coactivators and corepressors, collectively named coregulators. Therefore, the mutation or aberrant expression of sex steroid receptor coregulators will affect the normal function of the sex steroid receptors and hence may participate in the development and progression of the cancers.
Highlights
The mammary gland, the ovary and the uterus in females, and the testis and the prostate gland in males are the main target tissues of sex steroid hormones including estrogen, progesterone, and androgen
These hormones exert their functions in the target tissues through their specific intracellular receptors, the estrogen receptors (ER), the progesterone receptors (PR) and the androgen receptor (AR), which belong to the nuclear re
The expression level of steroid receptor RNA activator (SRA) is higher in androgen-independent PC-3 cells compared with that of the androgen-dependent cell lines, DU-145 and LNCaP. These results suggested that both SRA and SRAP play an important role in nuclear receptor (NR)-mediated transcription in prostate cancer
Summary
The mammary gland, the ovary and the uterus in females, and the testis and the prostate gland in males are the main target tissues of sex steroid hormones including estrogen, progesterone, and androgen. The development of resistance to hormonal replacement therapy for either breast or prostate cancers is related to aberrant expression, mutation of the genes and abnormal functioning of the respective steroid receptors. The members of the SRC family interact with steroid receptors, ER, PR and AR, and enhance their transcriptional activation in a ligand-dependent manner [5].
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