estrone-sulfate and Carcinoma

Spontaneous canine mammary inflammatory carcinoma (IMC) shares epidemiologic, histopathologic and clinical characteristics with the inflammatory breast carcinoma (IBC) disease in humans. We have analysed the steroids levels in serum and in tissue homogenates of IMC, the expression of two of their receptors (androgen and beta-estrogen) and of three enzymes included in the steroidogenesis pathway (aromatase (CYP19A1), steroid sulphatase (STS) and estrogen sulfotransferase (EST)) trying to explain the specific accumulation of steroids in IMC tissues generating deposits in the form of lipid droplets whose presence can be attributed to steroids secreted by IMC cells. According to our working hypothesis, oestrone sulphate would be the main component of these lipid droplets. The presence of these steroid deposits would contribute to the intense proliferation and invasive behaviour of IMC and IBC, although their involvement in angiogenesis is yet to be demonstrated.

Topics: Animals; Carcinoma; Dogs; Estrone; Female; Mammary Neoplasms, Animal; Mastitis; Signal Transduction; Steroids; Steryl-Sulfatase

Inflammatory mammary carcinoma (IMC) is the most aggressive spontaneous type of mammary malignant tumor both in women and dogs. Latest studies in dogs indicate that different endocrine mechanisms seem to be involved in inflammatory carcinomas (IMCs). The aim of the present study was to characterize the steroid hormone profile of inflammatory carcinoma, and to compare it with mammary dysplasias, benign tumors and other malignant tumors. Eighty-six mammary samples (10 normal mammary tissue, 21 dysplasias, 26 benign, 22 malignant, and 7 IMC) from 30 female dogs were used. Hormone levels of progesterone (P4), 17beta-estradiol (E2), androstenedione (A4), dehydroepiandrosterone (DHEA), and estrone sulphate (E1SO4) in tissue homogenates were measured by enzyme immunoassays (EIAs) techniques, previously validated for this species. IMC displayed the following steroid profile: P4: 13.80+/-0.56 microg/g; E2: 675.19+/-33.00 ng/g; A4: 631.73+/-70.73 microg/g; DHEA: 702.22+/-89.93 microg/g, and E1SO4: 2.84+/-0.32 mg/g. All of these hormones were significantly higher (P<0.001) compared with the hormone steroid profile determined for malignant, benign, dysplasias, and normal mammary tissue. The most relevant finding was the increased levels, two or three times, of both DHEA and E1SO4 in IMC respect to other groups (P<0.001). These results, together with the highest immunohistochemical expression of P450scc found in IMC, suggest the hypothesis that an autocrine mechanism could be especially involved in the development of canine inflammatory carcinoma.

Topics: Androstenedione; Animals; Carcinoma; Dehydroepiandrosterone; Dogs; Estradiol; Estrone; Female; Immunoenzyme Techniques; Immunohistochemistry; Inflammation; Mammary Neoplasms, Animal; Progesterone

The ability of breast tumors to synthesize sex steroid hormones is well recognized and their local production is thought to play a role in breast cancer development and growth. The aim of this study was to estimate local intra-tumoral and circulating levels of Estrone (E1), Estrone Sulfate (E1S), Estradiol (E2), Estriol (E3), and Testosterone (T) in 33 pre- and postmenopausal women with primary breast cancer in comparison to 12 pre- and postmenopausal women with benign breast tumors. The mean levels of the studied sex hormones were higher in serum and tumor tissue of breast cancer women than those with benign breast tumors apart from Testosterone which showed a significant decrease in pre- and postmenopausal women with breast cancer (P<0.001for follicular phase, P<0.05 for luteal phase, and P<0.005 for postmenopausal). The levels of the five hormones were significantly higher intra-tumoral than in serum of both benign and malignant breast tumor women with E1S as the predominant estrogen. There was only a positive significant correlation between serum and tumor tissue levels of E1 (rs=0.52, P<0.05 for follicular; rs=0.63, P<0.05 for luteal and rs=0.58, P<0.05 for postmenopausal) and a significant correlation between serum and tumor tissue of T (rs=0.64, P<0.05 for follicular; rs=-0.51, P<0.05 for luteal and rs=-0.81, P<0.04 for postmenopausal).

Topics: Adult; Aged; Biomarkers; Breast Diseases; Breast Neoplasms; Carcinoma; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Estradiol; Estriol; Estrone; Female; Fibroadenoma; Follicular Phase; Gonadal Steroid Hormones; Humans; Luteal Phase; Middle Aged; Postmenopause; Premenopause; Testosterone

The hydrolysis of dehydroepiandrosterone sulfate (DHAS) by human liver cells in culture and the hydrolysis of and formation of estradiol-17 beta (E2) from estrone sulfate (E1S) by human breast tumor preparations in vitro were studies in the presence and absence of danazol. In the latter tissue the effects of medroxyprogesterone acetate (MPA), trilostane, aminoglutethimide (AG) and tamoxifen were tested for comparison. Danazol at concentrations of 10(-6) - 1.4 X 10(-4) M strongly inhibited the hydrolysis of DHAS as well as the hydrolysis of and formation of E2 from E1S. With the exception of a slight inhibitory effect of trilostane upon E1S hydrolysis, the other four drugs did not inhibit the metabolism of E1S. Danazol, at concentrations corresponding to those occurring in vivo during therapy, is a potent inhibitor of steroid sulfatase activity. This may be one of the ways in which the drug affects peripheral and target tissue levels of steroid hormones.

Topics: Aminoglutethimide; Breast Neoplasms; Carcinoma; Culture Techniques; Danazol; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Dihydrotestosterone; Estrogen Antagonists; Estrone; Female; Humans; Medroxyprogesterone; Medroxyprogesterone Acetate; Pregnadienes; Tamoxifen