Sex hormone receptors in mammary tumours of GR mice

We have previously shown, in the estrogen-unresponsive C3H mouse mammary tumor that the affinity of the estrogen receptor (ER) for calf thymus DNA in vitro is four-times higher than that of uterine ER [Baskevitch, P. P., Vignon, F., Bousquet, C. and Rochefort, H. (1983) Cancer Res. 43,22901. By mixing cytosols from this tumor and uterus, we describe a tumor factor capable of increasing ER affinity for DNA, as assayed by DNA-cellulose chromatography and saturation studies. The activity of this factor was inhibited by a-chymotrypsin-inhibitors such as N-tosylphenylalanylchloromethane and chymostatin. Using the fluorogenic substrate glutarylglycylglycylphenylalanyl-N-naphthylamide, we assayed such a protease in the C3H mammary tumor cytosol. This protease and the factor altering ER-DNA binding were eluted together from chromatography on DEAE-cellulose, AcA 44, and carboline-agarose and were sensitive to the same inhibitors. The partially purified factor decreases the molecular mass of the estrogen receptor as seen by denaturing electrophoresis after covalent labelling of the ER with [3H]tamoxifen aziridine. We suggest that the increase of ER affinity for DNA and the decrease of ER molecular size are due to the same protease with an a-chymotrypsin-like specificity.Systems resistant to steroid hormones are useful in analyzing the sequence of hormone action, particularly the nuclear and DNA binding of the receptor-hormone complex, and in determining their biological significance [I]. In mammary tumors, estrogen resistance is mostly associated with the lack of assayable estrogen receptor sites [2]. However, in humans, 50% of breast cancers which possess estrogen receptor (ER-positive) do not respond to endocrine therapy. One possibility is that the ER are present, and are capable of binding the hormone, but are unable to transduce the message efficiently to chromatin. In this respect, hormone-resistant and ER-positive experimental mammary tumors are particularly interesting.We have investigated the ER system in the C3H mouse mammary carcinoma. This tumor is estrogen-unresponsive since in vivo estradiol is unable to increase the concentration of the progesterone receptor sites, and does not sustain tumor growth [3, 41. In this tumor, the ER is present at moderate concentrations (20 -40 fmol/mg cytosol protein) and, after estrogen binding, is translocated into the nucleus in vivo [3]. Therefore the estrogen-unresponsiveness of the tumor is not due to the absence of nuclear ER. It may therefore be the consequence of a post-receptor defect [5]. We have recently shown that the ER from C3H tumor has a fourfold higher affinity in vitro for non-specific DNA as compared to the ER

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“…This suggests that the independent GR/A tumor [7] contains a factor analogous to the one found in C3H tumor cytosol.…”

Section: Preliminury Distribution Of the Mammary Tumor Fuctormentioning

confidence: 76%

“…The GR/A mouse tumors were a gift of Dr M. Sluyser (Amsterdam, Netherlands); they were induced by a combined estrone-progesterone treatment [6] which was stopped 2 days before sacrifice. The hormone-dependent and hormone-independent tumors were selected after seriaj transplantations to the inbred host, as described [7].…”

Section: Tissuesmentioning

confidence: 99%

A cytosol protease from the estrogen-resistant C3H mammary carcinoma increases the affinity of the estrogen receptor for DNA in vitro

Baskevitch

Rochefort

1985

Eur J Biochem

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“…In the seventies, studies at the Netherlands Cancer Institute on Grunder mice established that mammary carcinomas are mixed populations of hormonedependent and hormone-independent tumor cells (1,2). The latter population could be selected for by transplanting mammary tumors into hormone nontreated castrated mice because, in the absence of estrogen and progesterone, only the hormone-independent subpopulations could form outgrowths.…”

Section: Chemo-hormonal Therapy Of Breast Cancer: Lack Of Interactionmentioning

confidence: 99%

“…Not wanting to take anything away from his otherwise excellent article, I do have a concern about his comments on the use of hydrazine sulfate for treatment of patients with cancer cachexia. He mentions that hydrazine was ''demonstrated to favorably influence the abnormal glucose in protein metabolism in cachectic cancer patients and to maintain or even increase body weight,'' with references to two articles by Chelebowski et al (2)(3) published in the 1980's. I would like to point out that in the second of the two articles (3), although more patients who received hydrazine gained weight than patients who received placebo, the exact amount of weight gain was apparently small and not included in the report.…”

mentioning

confidence: 99%

Chemo-Hormonal Therapy of Breast Cancer: Lack of Interaction Between Lab and Clinic

Sluyser¹

1998

JNCI: Journal of the National Cancer Institute

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“…The tumours are heterogeneous populations of hormone-dependent and -independent cells; the latter tend to become more numerous during serial transplantation (Sluyser & Van Nie, 1974;Sluyser et al, 1976). Hormonedependent mammary-tumour cells differ from their independent counterparts in hormone-receptor content (Sluyser & Van Nie, 1974;Sluyser et al, 1976; mammary-tumouir virus expression (Sluyser et al,1 977) glycolytic enzymes (Briand & Daehnfeldt, 1973) number of isoacceptor peaks of transfer RNA (Qutist et al, 1976a, b) and iodide uptake (Thorpe, 1976).…”

mentioning

confidence: 99%

Changes in concanavalin A-mediated agglutination of hormone-dependent mouse mammary tumour cells during serial transplantation

Sluyser¹,

Valk²,

Blitterswijk³

1980

Br J Cancer

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The concanavalin A-mediated agglutinability of GR mouse mammary tumour cells changes during serial transplantation of the tumours. Hormone-dependent cells in general have a lower agglutinability than hormone-independent cells. However, changes have also been observed in the histology of the tumours during serial transplantation, which as such may also alter the Con A-mediated agglutinability of the tumour cells. Images Fig. 1(a) Fig. 1(b) Fig. 1(c) Fig. 1(d) Fig. 1(e) Fig. 1(f)

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Sex hormone receptors in mammary tumours of GR mice

Cited by 68 publications

References 9 publications

A cytosol protease from the estrogen-resistant C3H mammary carcinoma increases the affinity of the estrogen receptor for DNA in vitro

A cytosol protease from the estrogen-resistant C3H mammary carcinoma increases the affinity of the estrogen receptor for DNA in vitro

Chemo-Hormonal Therapy of Breast Cancer: Lack of Interaction Between Lab and Clinic

Changes in concanavalin A-mediated agglutination of hormone-dependent mouse mammary tumour cells during serial transplantation

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