Incidence, growth and oestradiol-receptor levels of 7,12-dimethylbenz(a)anthracene-induced mammary tumours in rats: effects of neonatal sex steroids and oestradiol implants

Verhoeven, Guido; Vandoren, G.; Heyns, Walter; Kuhn, Er; Janssens, Jaak; Teuwen, Dirk E.; Goddeeris, P; Lesaffre, Emmanuel; Moor, P. De

doi:10.1677/joe.0.0950357

Cited by 12 publications

(6 citation statements)

References 22 publications

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“…Our findings are consistent with the fact that ligands can alter the number/function of a receptor when they are present, and generally do not cause any persistent changes in receptor expression. One exception is an exposure that occurs during fetal life or immediately after birth, which can produce a permanent change (Verhoeven et al, 1982;Bern et al, 1985;Hilakivi-Clarke et al, 1998). However, since a prepubertal treatment with both a low (interacts with ER) and high (interacts with ER and other targets) dose of genistein or zearalenone reduces subsequent mammary tumorigenesis, prepubertal ERs may be involved as mediators of these effects.…”

Section: Discussionmentioning

confidence: 99%

Prepubertal exposure to zearalenone or genistein reduces mammary tumorigenesis

et al. 1999

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Prepubertal exposure to a pharmacological dose (500 mg kg −1 ) of the phyto-oestrogen genistein can reduce the incidence and multiplicity of carcinogen-induced mammary tumours in rats. However, such an exposure also disrupts the function of the hypothalamic–pituitary–gonadal axis, making it unsuitable for breast cancer prevention. We studied whether prepubertal exposure to genistein at a total body dose broadly comparable to the level typical of Oriental countries, approximately 1 mg kg −1 body weight, affects mammary tumorigenesis. We also studied whether prepubertal exposure to zearalenone, a major source for phyto-oestrogens in the USA, influences breast cancer risk. Prepubertal rats were treated between postnatal days 7 and 20, with 20 μg (~ 1 mg kg −1 body weight) of either genistein or zearalenone. Zearalenone exposure significantly reduced both the incidence and multiplicity of mammary tumours induced by 7,12-dimethylbenz(a)anthracene (DMBA). Genistein exposure significantly reduced tumour multiplicity, but not tumour incidence, when compared with vehicle-treated animals. Furthermore, 60% of the tumours in the genistein group were not malignant, while all the tumours analysed for histopathology in the vehicle and zearalenone groups were adenocarcinomas. A higher number of differentiated alveolar buds, and lower number of terminal ducts, were present in the DMBA-treated mammary glands of the phyto-oestrogen exposed rats. The concentration of oestrogen receptor (ER) binding sites after the DMBA treatment was low in the mammary glands of all groups but a significantly higher proportion of the glands in the zearalenone exposed rats were ER-positive (i.e. ER levels ≥ 5 fmol mg −1 protein) than the glands of the vehicle controls. Our data suggest that a prepubertal exposure to a low dose of either zearalenone or genistein may protect the mammary gland from carcinogen-induced malignant transformation, possibly by increasing differentiation of the mammary epithelial tree. © 1999 Cancer Research Campaign

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Section: Discussionmentioning

confidence: 99%

Prepubertal exposure to zearalenone or genistein reduces mammary tumorigenesis

et al. 1999

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“… Yoshida and colleagues [ 55 ] SD rats TP 1.25 Daily until the end of the experiment ? Purnell [ 56 ] LEW/Mai rats TP 1.25 Single injection No effect Verhoeven and colleagues [ 57 ] Female and male SD rats TP 0.5 Single injection No effect SD, Sprague?Dawley; TP, testosterone propionate. a Female rats unless otherwise specified.…”

Section: Effects Of Androgens In Rodent Breast Cancer Modelsmentioning

confidence: 99%

“…DMBA-induced tumor incidence has also been examined after neonatal androgenization of female rats (Table? 3 ) [ 52 ]-[ 57 ], with androgens first injected between 0 to 5?days after birth and treatment varying from a single injection to continuous treatment until the end of the experiment. Most studies [ 52 ]-[ 55 ], but not all [ 56 ],[ 57 ], found that, like peri-pubertal treatments, neonatal androgenization reduced tumor incidence.…”

Section: Effects Of Androgens In Rodent Breast Cancer Modelsmentioning

confidence: 99%

The role of androgens in experimental rodent mammary carcinogenesis

et al. 2014

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Breast cancer is currently the most frequent, fatal cancer of women in western countries. While estrogens have a widely understood involvement in breast cancer, a significant but not yet fully understood role for androgens has also been suggested. The principal androgen, testosterone, is the obligate steroidal precursor of estradiol, but can equally be metabolized into dihydrotestosterone, a more potent, pure androgen. Both androgens exert their distinctive biological effects via the androgen receptor, which is coexpressed with estrogen receptor alpha in 80 to 90% of breast cancers. The hormonal control of breast development and pathology has been examined experimentally through the use of animal models, notably mice and rats. This review summarizes the data from experimental rodent models on the effects of androgens in experimental breast cancer, aiming to address the importance of androgens and the androgen receptor in the origins and pathogenesis of breast cancers, as well as to discuss potential biomarker and therapeutic opportunities arising from novel insights based on the experimental research.

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“…Verhoenven et al performed gonadectomy to neonatal male and female rats and immediately treated some of the animals with a single dose of T or E2 [98]. These animals did not show significant change in the incidence of DMBA-induced mammary carcinomas, compared to the gonadectomized rats without treatment of T or E2.…”

Section: Uses Of Androgens In Womenmentioning

confidence: 99%

Mechanisms for c-myc Induced Mouse Mammary Gland Carcinogenesis and for the Synergistic Role of TGF(alpha) in the Process

Liao¹

2001

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructior's, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302, and ABSTRACT (Maximum 200 Words)This project aims to elucidate the cell cycle basis on which c-myc oncogene induces mammary carcinogenesis and transforming growth factor o (tgfcx) promotes the process. Conduction of this training project will help the P.1. to develop his career in breast cancer research. Data obtained so far have shown that c-myc transgenic mammary tumors may develop specific foci that are more aggressive than their adjacent tumor areas and thus represent a second stage of tumor progression. c-Myc may induce E2F1 and cyclin A2 to initiate the tumor development, whereas overexpression of cyclins DI and E may occur as later events to promote tumor progression to a more aggressive phenotype. TGFcc may enhance c-Myc-induced mammary carcinogenesis by inducing cyclin DI and facilitating the loss of pRB expression, resulting in an earlier development of more aggressive tumors in tgfa/c-myc double transgeneic mice, compared to the c-myc tumors. These findings in the transgenic animals may have relevance to human breast cancer. INTRODUCTION:This subject of study aims to elucidate the cell cycle basis on which c-myc oncogene initiates mammary carcinogenesis and transforming growth factor (X (tgfa) promotes the process. Conduction of this training project will help the P.I., Dr. Dezhong Liao, to develop his career in breast cancer research. This research project has four tasks, each of which is consisted of two parts, i.e. in vivo studies with transgenic mice and in vitro studies with cultured cells. The four tasks are: "* Task 1. Study whether expression of E2F1 and cyclin A2 is induced to mediate mammary cancer formation in c-myc mice. (Months 1-15). "* Task 2. Investigate whether c-myc initially suppresses cyclin DI expression, but overexpression of cyclins DI and E occurs as later events to facilitate progression of tumors to faster growing phenotypes. (Months 1-15) "* Task 3. Study the mechanisms and the roles of overexpression of cyclins DI and E in mammary carcinogenesis in TGFc/c-myc mice. . "* Task 4. Investigate the mechanisms for the loss of pRB during mammary carcinogenesis in myc and TGFcu/c-myc mice. BODY:1. In vivo animal experiments on the cell cycle basis of c-myc-induced, tgfu.-enhanced mouse mammary carcinogenesis: We have actually started the project since this proposal was submitted to DOD in June of 1999, about one year earlier than the time when the award was started. During the past two years, ...

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Incidence, growth and oestradiol-receptor levels of 7,12-dimethylbenz(a)anthracene-induced mammary tumours in rats: effects of neonatal sex steroids and oestradiol implants

Cited by 12 publications

References 22 publications

Prepubertal exposure to zearalenone or genistein reduces mammary tumorigenesis

Prepubertal exposure to zearalenone or genistein reduces mammary tumorigenesis

The role of androgens in experimental rodent mammary carcinogenesis

Mechanisms for c-myc Induced Mouse Mammary Gland Carcinogenesis and for the Synergistic Role of TGF(alpha) in the Process

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