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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To test the hypothesis of an increased activity of the enzyme aromatase in adipose tissue from affected when compared with non-affected quadrants of patients with breast cancer, the aromatase activity has been measured in tumour and fatty tissues dissected at specific sites from the breasts of 16 patients. Activity was measured after extensive purification of the product formed. Results, expressed in fmol/g of tissue, did not show a higher activity in the affected vs the non-affected quadrants. In the tumours, higher activities were found when expressed per g of tissue. Per mg of DNA, an indicator of the number of cells, tumour enzymatic activity was lower than in fatty tissues. The relations between the products of aromatase, oestrone and oestradiol in the various tissues point to the importance of additional enzymatic processes, especially of the reductive 17 beta-oestradiol dehydrogenase, in the accumulation of high quantities of oestradiol in the malignant tissue.
J Steroid Biochem Mol Biol 1991 Nov
PMID:Endogenous steroid hormones and local aromatase activity in the breast. 195 69

The most important mitogen for human breast cancer is oestrogen. Since oestrogens are synthesized via a protracted series of enzymic conversions from cholesterol, there are many potential targets for inhibition which could theoretically lead to suppression of oestrogen synthesis. However, inhibition of many of these targets is complicated by a resultant interference in the synthesis of other steroids, particularly glucocorticoids. This results in inhibitors of aromatase being the most rational choice for oestrogen suppression in breast cancer patients. Several aromatase inhibitors are in clinical usage. It is important that the clinical effectiveness of these is compared with that of the antioestrogen, tamoxifen.
J Steroid Biochem Mol Biol 1991 Nov
PMID:Inhibitors of steroidogenic enzymes for the treatment of breast cancer. 195 70

Oestrogens and progestins are important for both the genesis of human breast cancer and growth of those tumours once formed. Their role at different stages of the neoplastic process are reviewed and discussed within the context of a change in sensitivity of epithelial cells during either initiation or promotion stages. Evidence favours, but does not conclusively prove, the view that progestins are the predominant mitogen for normal breast epithelium whilst oestrogen assumes that function in neoplastic epithelium. Alterations in oestrogen receptor levels could provide the key for such a change. There are insufficient data on physiological progestin concentrations to judge their effect on established cancer. Models for steroidal effects on cell proliferation and oestrogen and progestin receptor regulation that are based on endometrial data are not appropriate for breast.
J Steroid Biochem Mol Biol 1991 Nov
PMID:A discussion of the roles of oestrogen and progestin in human mammary carcinogenesis. 195 71

We determined the effects of epidermal growth factor, insulin-like-growth-factor-1 and estradiol on the anchorage independent growth of the estrogen receptor positive human breast cancer cell lines MCF7 and T-47D. In serum free conditions growth factors but not estrogen induced a dose dependent stimulation of growth in both cell lines. The ability of estrogen to induce colony formation of early passage MCF7 cells (less than 100) was strictly correlated to the concentration of sulfatase and charcoal treated calf serum (CCS) with a maximal effect at a concentration of 5% CCS and 10 nM estradiol. CCS alone had no stimulatory effect on the anchorage independent growth of early passage MCF7 cells, but increased colony formation in late passage (greater than 1000) MCF7 and T-47D cells. The growth of late passage MCF7 cells was inhibited by antiestrogen. Thus, the presence of serum components is necessary for the effect of estrogen but not for the effects of growth factors on the anchorage independent growth of estrogen receptor positive human breast cancer cell lines; after a prolonged period of tissue culture serum components switch their function from indirectly modulating estrogen effects to directly stimulating growth in the absence of estrogen.
J Steroid Biochem Mol Biol 1991 Nov
PMID:Tissue culture conditions determine the effects of estrogen and growth factors on the anchorage independent growth of human breast cancer cell lines. 195 6

Therapeutic strategies for human breast cancer using 125I-labeled steroid hormones are clinically attractive in light of the estrogen dependence of many human breast cancers and the favorable microdosimetry resulting from 125I decay. We determined the uptake specific estrogen receptor binding and radiotoxicity of 17 alpha-[125I]iodovinyl-11 beta-methoxyestradiol (125IVME2) in vitro using cultured MCF-7 human breast carcinoma cells. 125IVME2 rapidly enters MCF-7 cells and reaches a plateau in the presence of competing 10(-7) M 17 beta-estradiol. In the absence of competitor, uptake is substantially greater before reaching a plateau. Efflux of 125IVME2 from cells incubated in the absence of estradiol decreases to levels corresponding to specific binding. Under equilibrium conditions and in the absence of competitor, 125IVME2 binds to both specific and nonspecific sites but, in the presence of excess 17 beta-estradiol, the observed binding is nonspecific. 125IVME2 is cytotoxic to exponentially growing MCF-7 cells and produces a survival curve typical of those observed for [125I]iododeoxyuridine and 16 alpha-[125I]iodoestradiol.
J Steroid Biochem Mol Biol 1991 Nov
PMID:Radiotoxicity of 17 alpha-[125I]iodovinyl-11 beta-methoxyestradiol in MCF-7 human breast cancer cells. 195 9

Activity of NAD-dependent 17 beta-hydroxysteroid dehydrogenase (E2DH), the enzyme which converts estradiol (E2) into its less active metabolite estrone (E1), has been previously characterized in normal human breast cells in culture and in benign and malignant breast tumors. E2DH activity is far greater in epithelial cells than in fibroblasts. Moreover, it is progesterone dependent in epithelial cells. It was therefore interesting to explore E2DH in the progesterone receptor (PR)-rich T47D cell line as a possible marker of hormone dependence in breast cancer cells. In T47D cells, transformation of [3H]E2 to E1 is limited. The metabolism seems to be preferentially oriented in the way E1----E2 in these cells. However, in the presence of the cofactor NAD the conversion of E2 into E1 increases. Moreover, treatment of T47D cells in culture by the progestin R5020 stimulates E2 to E1 conversion 2- to 3-fold. Stimulation of E2DH (E2----E1) activity reflects both the presence and the operability of PR. This observation underlines the possible interest of E2DH assay in parallel to estradiol receptor and PR to evaluate hormone-dependence of breast cancer.
J Steroid Biochem Mol Biol 1991 Nov
PMID:17 beta-estradiol dehydrogenase (E2DH) activity in T47D cells. 195 11

Over the last 2 decades epidemiologists have increasingly used parameters of endocrine function in their studies. Prospective cohort studies offer methodological advantages in view of the latency between the relevant hormonal exposure and the clinical onset of cancer. Examples from the author's experience are provided. Evidence is mounted for an important "time window" for breast cancer development between menarche and the birth of a first child.
J Steroid Biochem Mol Biol 1991
PMID:Endocrine aspects of cancer: an epidemiological approach. 195 15

It has been previously shown that estrogens may exert their action on human breast cancer cells through coordinated control of secreted growth factors which act in an autocrine and paracrine fashion. Growth stimulation of the androgen receptor negative prostate carcinoma cell line DU-145 by dihydrotestosterone in the presence of the androgen-responsive human prostate carcinoma cell line LNCaP now indicates that androgens may regulate growth of prostate carcinoma cells through related mechanisms. A variety of androgen-regulated growth modulatory activities with autocrine and paracrine potential can be detected in conditioned media from LNCaP cells partially purified by ion exchange chromatography. Androgen-induced growth of LNCaP cells is partially inhibited by the polyanions suramin and dextran sulfates which antagonize growth factor action. These data suggest the existence of at least two different mechanisms of growth regulation by androgen which can be distinguished by their different sensitivity to growth factor inhibitory agents. We conclude that the combination of antipeptidergic substances and androgen withdrawal would represent a new and promising strategy for treatment of human prostate cancer.
J Steroid Biochem Mol Biol 1991
PMID:Growth factors in human prostate cancer cells: implications for an improved treatment of prostate cancer. 195 19

We have studied the mechanism by which 17 beta-oestradiol (E2) stimulates breast cancer proliferation using the MCF7 cell line as a model system. We provide evidence that E2 directly stimulates cellular proliferation by inducing, like many growth factors, the c-fos proto-oncogene. E2 by itself, however, is poorly mitogenic and it does not induce genes from the jun family, whose gene products are necessary for heterodimerization with the c-fos encoded protein (Fos), leading to an important step in growth factor signalling pathways, stimulation of the 12-O-tetradecanoyl-phorbol-13-acetate responsive element (TRE)-dependent transcriptional activity. In combination with insulin-like growth factors (IGFs), efficient inducers of c-jun in breast cancer cells, E2 synergistically stimulates TRE-activity and proliferation. This direct stimulation by E2 of growth factor signalling pathways suggest that E2 can directly induce proliferation, independent from autocrine growth factors.
J Steroid Biochem Mol Biol 1991
PMID:Oestrogen directly stimulates growth factor signal transduction pathways in human breast cancer cells. 195 24

The cathepsin D gene is differentially regulated by estrogens in hormone responsive breast cancer cells, by progestins in normal human endometrium and is highly expressed but not regulated by these steroids in estrogen (RE)- and progesterone receptor (RP)-negative breast cancer cells. We have stably transfected the RE-negative breast cancer cell line MDA-MB 231 and the Hela cell line with an expression vector for the human RE. The endogenous cathepsin D which is constitutively expressed was further stimulated by estradiol. However, the growth of both cell lines was not stimulated by estradiol and could not be inhibited by the antiestrogen ICI 164,384. By contrast, the cathepsin D gene in the estrogen responsive Ishikawa endometrial cancer cell line was unresponsive to estrogen or to progesterone even following stable transfection of expression vectors for the RP (both A and B isoforms). We conclude that the cathepsin D gene is potentially responsive to estrogens in MDA-MB 231 and Hela cells, which therefore express all of the transcriptional machinery (except the RE) necessary for this regulation. By contrast, cathepsin D remains unresponsive to estrogen and progesterone in Ishikawa cells. The cathepsin D gene is one of the first examples of an endogenous steroid responsive gene which can be controlled by steroids following stable transfection of a steroid receptor.
J Steroid Biochem Mol Biol 1991
PMID:Hormonal regulation of cathepsin D following transfection of the estrogen or progesterone receptor into three sex steroid hormone resistant cancer cell lines. 195 26


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