ABSTRACT
It is known that the steroid sulfatase (STS) and the estrogen sulfotransferase (EST1E1) are commonly expressed in human breast carcinomas. STS and EST1E1 combined action could maintain the equilibrium between sulfated (inactive) and unconjugated (active) estrogens, which might have effects on development of hormone dependent breast cancer.We studied the expression of the STS and EST1E1 in 88 breast carcinomas and 57 adjacent non-malignant tissues by immunohistochemistry. The results were correlated with the tumor expression of estrogen receptor α (ER-α) and ß (ER-ß), progesterone receptor A (PR-A) and B (PR-B) and the proliferation marker CDC47, the tumoral type and stage and the age at surgery.STS expression was higher in carcinoma specimens than in adjacent normal tissues, although not to a significant level (p = 0.064) and it was positively associated with CDC47 expression (p < 0.05). These observations support the hypothesis that STS is overexpressed in breast cancer and associated with a worse prognosis.EST1E1 was observed for the first time in the nuclei of epithelial and tumoral cells. Tumor expression of EST1E1 was positively correlated with ER-ß (p < 0.01) and PR-B (p < 0.05), two steroid receptors already associated with an improve prognosis for breast cancer.Controlling the STS overexpression in carcinomas could be a way to inhibit cancer growth. The significance of the association between EST1E1 and ER-ß or PR-B should be further studied since these two receptors are transcription activators and may regulate the expression of protective enzymes like EST1E1.
ABSTRACT
Estrogens play an important role in the development and progression of breast cancer. 17beta-Hydroxysteroid dehydrogenase (17beta-HSD) type 2 and type 5 are involved in sex steroid metabolism. 17beta-HSD type 2 converts estradiol to estrone while 17beta-HSD type 5 converts androstenedione to testosterone. Using immunocytochemistry, we have studied the expression of 17beta-HSD type 2 and type 5 in 50 specimens of breast carcinoma and adjacent non-malignant tissues. The results were correlated with the estrogen receptor alpha (ERalpha) and beta (ERbeta), progesterone receptor A (PRA) and B (PRB), androgen receptor and CDC47 and with the tumor stage, tumor size, nodal status and menopausal status. 17beta-HSD type 2 was expressed in 20% and 17beta-HSD type 5 in 56% of breast cancer specimens. In adjacent normal tissues, both enzymes were highly expressed in almost all the patients. No significant association could be found between the expression of 17beta-HSD type 2 and 17beta-HSD type 5 and between the expression of each enzyme and the clinicopathological parameters studied. The decrease in 17beta-HSD type 2 and 17beta-HSD type 5 expressions in breast cancer may play a predominant role in the development and/or progression of the cancer by modifying the intratumoral levels of estrogens and androgens.
Subject(s)
17-Hydroxysteroid Dehydrogenases/biosynthesis , Breast Neoplasms/enzymology , Breast Neoplasms/pathology , Breast/enzymology , 3-Hydroxysteroid Dehydrogenases , Adult , Aged , Aldo-Keto Reductase Family 1 Member C3 , Animals , Estradiol Dehydrogenases , Estrogen Receptor alpha/biosynthesis , Estrogen Receptor beta/biosynthesis , Female , Humans , Hydroxyprostaglandin Dehydrogenases , Middle Aged , Rabbits , Receptors, Androgen/biosynthesis , Receptors, Progesterone/biosynthesisABSTRACT
BACKGROUND: Estrogen is recognized to play a role in the development and function of the prostate. Estrogen sulfotransferase (EST) 1E1 catalyzes the sulfoconjugation of estrogen and is thus involved in the metabolism of estrogen. We have recently shown that EST 1E1 is highly expressed in male mouse reproductive organs, including prostate. It appeared of interest to study the expression of EST 1E1 in human prostate. METHODS: EST 1E1 mRNA and protein expression was evaluated in benign prostatic hyperplasia (BPH) using in situ hybridization and immunocytochemistry, respectively. RESULTS: EST 1E1 mRNA and protein were found to be expressed in epithelial cells bordering alveola lumen (luminal cells) as well as stroma cells. CONCLUSION: The enzyme EST may play a physiological role in regulating local estrogen levels in human prostate.
