Effects of progesterone on mammary carcinogenesis by DMBA applied directly to rat mammae

Jabara, Anne G.; Marks, Guido; Summers, JL; Anderson, Patricia S.

doi:10.1038/bjc.1979.175

Cited by 12 publications

(4 citation statements)

References 14 publications

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“…Tumor-promoting effects of progesterone are also observed in rodents, where chemically (7,12-Dimethylbenzanthracene)-induced carcinogenesis is enhanced/accelerated by progesterone/progestin administration (73,74). In support of this model, pharmacologically or genetically blocking RANKL delayed tumorigenesis (47,75).…”

Section: Tumor-promoting Action Of Progesteronementioning

confidence: 85%

Progesterone and Overlooked Endocrine Pathways in Breast Cancer Pathogenesis

2015

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Worldwide, breast cancer incidence has been increasing for decades. Exposure to reproductive hormones, as occurs with recurrent menstrual cycles, affects breast cancer risk, and can promote disease progression. Exogenous hormones and endocrine disruptors have also been implicated in increasing breast cancer incidence. Numerous in vitro studies with hormone-receptor-positive cell lines have provided insights into the complexities of hormone receptor signaling at the molecular level; in vivo additional layers of complexity add on to this. The combined use of mouse genetics and tissue recombination techniques has made it possible to disentangle hormone action in vivo and revealed that estrogens, progesterone, and prolactin orchestrate distinct developmental stages of mammary gland development. The 2 ovarian steroids that fluctuate during menstrual cycles act on a subset of mammary epithelial cells, the hormone-receptor-positive sensor cells, which translate and amplify the incoming systemic signals into local, paracrine stimuli. Progesterone has emerged as a major regulator of cell proliferation and stem cell activation in the adult mammary gland. Two progesterone receptor targets, receptor activator of NfκB ligand and Wnt4, serve as downstream paracrine mediators of progesterone receptor-induced cell proliferation and stem cell activation, respectively. Some of the findings in the mouse have been validated in human ex vivo models and by next-generation whole-transcriptome sequencing on healthy donors staged for their menstrual cycles. The implications of these insights into the basic control mechanisms of mammary gland development for breast carcinogenesis and the possible role of endocrine disruptors, in particular bisphenol A in this context, will be discussed below.

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Section: Tumor-promoting Action Of Progesteronementioning

confidence: 85%

Progesterone and Overlooked Endocrine Pathways in Breast Cancer Pathogenesis

2015

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“…* Data indicate the average ± standard deviation , and were statistically significant difference (p<0.01) from the control MFP. The local action of hormones on DMBA mammary carcinogenesis in the rat, when a small dose of the carcinogen with or without the hormone was applied directly to the mammary fatty pad, has been investigated (7,17). Shinha and Dao (18) reported later that microscopic tumors originated in the ducts as early as 30 days after the local application of carcinogen without previous development of hyperplastic alveolar nodules.…”

Section: Resultsmentioning

confidence: 99%

Dehydrogenases in Local Carcinogenesis in Rat Mammary Gland by Dusting of Dmba-Powder

Morii

Tsubura

Takaoka

et al. 1980

Acta Histochem. Cytochem

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To the 5th right mammary gland of Sprague-Dawley female rats, ca 1 mg of DMBA was directly administered by means of a dusting of its pure powder over the mammary fatty pad. At the site of administration, a nodule of adenocarcinoma was induced more than 7 weeks after the local application with high incidence.It was enhanced more in the adults than the youngs. Histochemically, atypisms of ALP and LDH activities were observed on the apparent malignant tissues induced by DMBA-dusting. Biochemical observations on the activities of LDH and MDH and on the pattern of LDH isoenzymes were done for the induced nodules with DMBA-dusting over females aged 8-26 weeks, which were harvested 5-18 weeks after the local application. The quotients of LDH/MDH in the same sample elevated on the malignant tissues prominently owing to higher LDH activity, and the elevation was moderate on the earlier-harvested, granulomatous tissues. But, the shift toward predominance of the M type of LDH was detected distinctly in the earlier granulomatous samples harvested 5 weeks after the local application.Mammary tissues of the rat are foremost among cells of mammals in terms of susceptibility to the induction to cancer by 7,12-dimethylbenz (a) anthracene (DM BA). Mammary adenocarcinoma rapidly becomes evident in young adult SpragueDawley females administered with a pulse dose (6). But the site of initiation and early changes of carcinogenesis cannot be pointed out so soon in experiments of such systemic administration.Shinha and Dao (17) developed a technique for inducing mammary tumors by direct application of a minute quantity of DMBA. The location of early carcinogenesis might be indicated immediately after the administration of carcinogen in this experimental design. In the present paper, the mammary tumorigenesis by local application of DMBA into females aged 6-26 weeks was observed histopathologically, and then histo-and bio-chemical observations on some enzymic activities were serially done in the carcinogenesis with DMBA-dusting over the mammary fatty pads of adult females, in comparison with control mammary fatty pads, spontaneously occurring mammary fibroadenomas and induced mammary adenocarcinomas with pulse doses of DMBA.

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“…Based on this results, the researcher assume that cancer induction by carcinogen compounds DMBA and Estradiol for 2 months has not resulted in excessive inflammatory reactions to cause cachexia syndrome. In rats model, DMBA can cause cachexia after 195 days of administration, while in 1 month administration of DMBA was not enough to promote cachexia syndrome [42,43]. TNF-α is cytokines that play major role to cause cachexia syndrom, and the increasing number of TNF-α can be considered as cachexia symtomps, because TNF-α responsible to degradation of myofibrillar and soleus muscle proteins [44].…”

Section: Issnmentioning

confidence: 99%

The Effect of E. scaber Extract to TNF-α and TGF-β on Mice under Carcinogen Treatment

Amalia

Widyarti

Djati

2018

JELS

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Carcinogen compounds are the compounds that cause DNA damage and trigger cancer. TNF-α and TGF-β are cytokines produced by immune cells and serve to maintain body homeostasis. Elephantopus scaber is a plant that prevents the cancer progression, and improve the body's immune system, so this study was conducted to determine the effect of E. scaber extract on TNF-α and TGF-β after the administration of carcinogen compounds. The study was conducted by administering the carcinogen compound DMBA with a dosage of 0.56 mg kg-1 BW and estradiol with a dose of 0.0504 mg kg-1 BW which was given alternately for 8 weeks to the Mus musculus test animals. The study was conducted in 3 groups: K-(the normal group of mice), K + (a carcinogen-induced group of mice), and P (a group of carcinogen-induced mice and E. scaber extract). The treatment was done in 1 week, 2 weeks, and 3 weeks. Immune cells were isolated from splenocytes and performed immunostaining for flow cytometry analysis. The computed relative amount is TNF-α produced by macrophages CD11b and TGF-β produced by Treg CD4CD25. The relative number of cells was analyzed by two-way ANOVA and advanced Tukey test with 95% confidence level (α = 0.05). The results showed no significant differences in the number of cytokines TNF-α and TGF-β in both the carcinogen-induced mice group and the mice group was given the extract of Elephantopus scaber for 1 week, 2 weeks and 3 weeks.

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Effects of progesterone on mammary carcinogenesis by DMBA applied directly to rat mammae

Cited by 12 publications

References 14 publications

Progesterone and Overlooked Endocrine Pathways in Breast Cancer Pathogenesis

Progesterone and Overlooked Endocrine Pathways in Breast Cancer Pathogenesis

Dehydrogenases in Local Carcinogenesis in Rat Mammary Gland by Dusting of Dmba-Powder

The Effect of E. scaber Extract to TNF-α and TGF-β on Mice under Carcinogen Treatment

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