Receptors Reconsidered: A 20-Year Perspective

Jensen, Elwood V.; Greene, Geoffrey L.; Closs, Liselotte E.; DeSombre, Eugene R.; Nadji, Mehrdad

doi:10.1016/b978-0-12-571138-8.50006-8

Cited by 97 publications

(68 citation statements)

References 102 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The mediation of biological effects of oestrogen in the presence of low receptor concentrations has been observed in certain parts of the brain (Bettini et al, 1992) and several other organs (see Ciocca and Vargas-Roig, 1995 for review). It is now recognised that most, if not all, mammalian tissues contain small amounts of ER (Jensen et al, 1982), and it has been suggested that the very presence of high levels of ER should not be the sole definition of an oestrogen-target tissue. A target cell may not contain ER but may still be called a target if it is affected specifically and directly by oestrogen stimulation (Ciocca and Vargas Roig, 1995).…”

Section: Discussionmentioning

confidence: 99%

Oestrogen increases S-phase fraction and oestrogen and progesterone receptors in human cervical cancer in vivo

Bhattacharya

Redkar²,

Mittra³

et al. 1997

Br J Cancer

View full text Add to dashboard Cite

Summary Although cancer of the cervix is traditionally considered not to be responsive to steroid hormones, an in vitro study has reported that the addition of oestrogen increased cellular proliferation in a cervix cancer cell line that was inhibited by progesterone. We investigated whether the reported in vitro effects of oestrogen and progesterone on cellular proliferation can be replicated in locally advanced cervical cancer in vivo and whether these effects, if any, are related to oestrogen and progesterone receptor (ER and PgR) content of the tumour. One hundred post-menopausal patients with locally advanced cervical cancer were systematically allocated by rotation to the four treatment groups: (1) control group receiving no treatment; (2) ethinyl oestradiol 50 gg; (3) norethisterone 5 mg; (4) a combination of ethinyl oestradiol and norethisterone. Hormone treatment (five doses) was given orally every 12 h. Tissue biopsies were taken before and 12 h after the last hormone treatment. S-phase fraction (SpF) was measured by flow cytometry, and ER and PgR were measured by enzyme immunoassay. Results were analysed using two-factor analysis of variance, the factors being oestrogen -absent or present -and progesterone -absent or present. The main effects of oestrogen were increases in SpF, ER and PgR, which were statistically significant (P= 0.0056, 0.0009 and 0.01 respectively), indicating that there is much greater change in these three parameters in the presence of oestrogen (mean changes 7.808 %, 6.258 fmol mg-' and 12.716 fmol mg-' for SpF, ER and PgR respectively) than in its absence (mean change -1.986 %, -3.041 fmol mg-' and 1.736 fmol mg-' respectively). The progestogen main effect and the oestrogen -progestogen interaction were not significant. The rise in SpF, ER and PgR in the presence of oestrogen had a correlation coefficient with the initial ER values of -0.0565, -0.2863 and -0.1230 respectively, none being statistically significant, suggesting that the oestrogen actions were not strictly related to baseline ER concentrations. The combined median baseline ER and PgR values of the four groups were 1.48 fmol mg-' and 0.80 fmol mg-' respectively. Our results show that oestrogen is capable of increasing SpF in locally advanced cervical cancer in vivo and may help to revive interest in the use of oestrogen as a radiosensitizing agent in the treatment of this disease.Keywords: cervical cancer; S-phase fraction; oestrogen receptor; progesterone receptor; radiosensitisation Carcinoma of the cervix is the commonest cancer in women in the developing world where most patients present at advanced stages when treatment with radiotherapy is not very effective (Hoskins et al, 1993). At least two studies have used adjuvant oestrogen treatment in an attempt to increase sensitivity of squamous cell carcinoma of the cervix to radiation therapy (Runge, 1959;Sugimori et al, 1976). One of these studies reported a significantly better survival in stage III patients in whom oestrogen was administered before and during radi...

show abstract

Section: Discussionmentioning

confidence: 99%

Oestrogen increases S-phase fraction and oestrogen and progesterone receptors in human cervical cancer in vivo

Bhattacharya

Redkar²,

Mittra³

et al. 1997

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…In analogy to the 'twostep' model proposed for the mechanism of action of steroid hormones [ l l , 121, an accumulation of TCDD-receptor complexes in the cell nucleus following occupation of cytosolic receptor sites has been reported by several authors [13 -171. This classical 'two-step' model has been questioned, however, and some recent reports [18,191 suggest that unoccupied steroid hormone receptors as well as unoccupied TCDD receptors in the intact cell are contained in the nucleus, and that ligand binding merely strengthens this association of the receptor with nuclear structures. This issue is not yet settled, but it is generally accepted that either a nuclear translocation or a strengthening of the nuclear association of the TCDDreceptor complex is required for the increased rate of transcription of TCDD-regulated genes [20,21].…”

mentioning

confidence: 99%

Characterization of the DNA-binding properties of the receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin

et al. 1986

View full text Add to dashboard Cite

The DNA-binding properties of the receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were investigated using chromatography on DNA-cellulose columns. A maximal binding of about 40% of the total receptor complex to DNA-cellulose was observed. In order to interact with DNA, the receptor must first bind TCDD. A heat-activation step followed by gel permeation chromatography using Sephadex G-25 increased the binding of the cytosolic receptor to DNA. The DNA-binding ability of the receptor was almost lost following mild proteolysis using trypsin or a-chymotrypsin, although these treatments did not reduce its ligand binding capacity and had no apparent effect on its size. Furthermore, pre-treatment of the DNA-cellulose column with an intercalating drug, ethidium bromide, resulted in inhibition of the binding of the TCDD-receptor complex to DNA, indicating that not only electrostatic interactions but also the configuration of DNA are of importance in receptor-DNA interactions.In analogy to the endocrine model of gene regulation by steroid hormones, several lines of evidence indicate that intracellular, soluble receptor proteins are essential mediators of the biological responses produced by certain xenobiotics, i. e. halogenated or non-halogenated aromatic hydrocarbons One particularly striking and often-studied biochemical effect produced by TCDD and related compounds is their potency to induce specific isozymes of cytochrome P-450 and the associated monooxygenase activity aryl hydrocarbon hydroxylase [l , 41 together with several non-monooxygenase activities, e. g. UDP-glucuronyltransferase, NAD(P)H dehydrogenase (quinone) (formerly called DT-diaphorase) and ornithine decarboxylase [l]. Several studies have demonstrated that administration of TCDD or TCDD-like inducers leads to a large increase in translatable mRNAs encoding the TCDDinduced isozyme(s) of cytochrome P-450 [5 -71. By in vitro nuclear transcription studies, this process has been shown to reflect an increased rate of transcription of the specific cytochrome P-450 gene(s) [8-lo]. In analogy to the 'twostep' model proposed for the mechanism of action of steroid Correspondence to J.-A. Gustafsson, Institutionen for Medicinsk Naringslara, Huddinge Sjukhus, F69, S-141 86 Huddinge, SwedenAbbreviations. TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDBF, 2,3,7,8-tetrachlorodibenzofuran; Azso -310 unit, the amount of material giving an absorbance at 280nm of 1 more than the absorbance at 310 nm in a 1 -cm pathlength cell; DCC, dextran-coated charcoal.Enzymes (IUB Recommendations 1984). Aryl hydrocarbon hydroxylase (EC 1.14.14.1); a-chymotrypsin (EC hormones [ l l , 121, an accumulation of TCDD-receptor complexes in the cell nucleus following occupation of cytosolic receptor sites has been reported by several authors [13 -171. This classical 'two-step' model has been questioned, however, and some recent reports [18, 191 suggest that unoccupied steroid hormone receptors as well as unoccupied TCDD receptors in the intact cell are contained in the nucleus, and ...

show abstract

“…In such cases hormonal therapy provides an objective benefit. The failure of 30-40% of patients with oestradiol receptor (ER)-rich tumours to respond to endocrine therapy was ascribed to either tumour heterogeneity or absence of progesterone receptor (PR) (McGuire et al, 1978;Jensen et al, 1982). Determination of PR content improves the diagnosis of hormone dependence (Horwitz et al, 1975), but about 20% of ER-positive, PR-positive tumours do not respond to hormone therapy.…”

mentioning

confidence: 99%

pS2 and response to adjuvant hormone therapy in primary breast cancer

Spyratos

Andrieu²,

Hacène³

et al. 1994

Br J Cancer

View full text Add to dashboard Cite

Summary We reviewed 319 primary breast tumours for cytosolic pS2 content, with a median follow-up of 6 years. pS2 status correlated positively with oestradiol and progesterone receptors and negatively with Scarff, Bloom and Richardson grade. pS2 positivity was associated with longer overall survival, particularly in patients who received hormone therapy, in whom pS2 status was also predictive of the response to therapy.

show abstract

Receptors Reconsidered: A 20-Year Perspective

Cited by 97 publications

References 102 publications

Oestrogen increases S-phase fraction and oestrogen and progesterone receptors in human cervical cancer in vivo

Oestrogen increases S-phase fraction and oestrogen and progesterone receptors in human cervical cancer in vivo

Characterization of the DNA-binding properties of the receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin

pS2 and response to adjuvant hormone therapy in primary breast cancer

Contact Info

Product

Resources

About