Prognostic factors in MNU and DMBA-induced mammary tumors in female rats

Alvarado, Antonieta; Lopes, Ana Cristina Macário; Faustino-Rocha, Ana I.; Cabrita, António Silvério; Ferreira, Rita; Oliveira, Paula A.; Colaço, Bruno

doi:10.1016/j.prp.2017.02.014

Cited by 49 publications

(47 citation statements)

References 25 publications

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“…The advantages of this model are the strong tumorigenic properties of the cells and a relatively short duration, within 7–10 days, of tumor development. This is a significantly shortened experimental protocol compared to the 8–10 weeks of tumor latency in chemically induced [methyl- N -nitrosourea (MNU) and DMBA] mammary carcinogenic models ( Abbasalipourkabir et al, 2010 ; Karimian et al, 2015 ; Alvarado et al, 2017 ). Not only is the LA7 model a faster method of tumor induction, but it is also ideally suited for testing therapies specifically targeting late stage carcinogenesis (progression) while circumventing the earlier phases.…”

Section: Introductionmentioning

confidence: 99%

Chemoprevention of LA7-Induced Mammary Tumor Growth by SM6Met, a Well-Characterized Cyclopia Extract

et al. 2018

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Breast cancer (BC) is the leading cause of cancer-related deaths in women. Chemoprevention of BC by using plant extracts is gaining attention. SM6Met, a well-characterized extract of Cyclopia subternata with reported selective estrogen receptor subtype activity, has shown tumor suppressive effects in a chemically induced BC model in rats, which is known to be estrogen responsive. However, there is no information on the estrogen sensitivity of the relatively new orthotopic model of LA7 cell-induced mammary tumors. In the present study, the potential chemopreventative and side-effect profile of SM6Met on LA7 cell-induced tumor growth was evaluated, as was the effects of 17β-estradiol and standard-of-care (SOC) endocrine therapies, such as tamoxifen (TAM), letrozole (LET), and fulvestrant (FUL). Tumor growth was observed in the tumor-vehicle control group until day 10 post tumor induction, which declined afterward on days 12–14. SM6Met suppressed tumor growth to the same extent as TAM, while LET, but not FUL, also showed substantial anti-tumor effects. Short-term 17β-estradiol treatment reduced tumor volume on days prior to day 10, whereas tumor promoting effects were observed during long-term treatment, which was especially evident at later time points. Marked elevation in serum markers of liver injury, which was further supported by histological evaluation, was observed in the vehicle-treated tumor control, TAM, LET, and long-term 17β-estradiol treatment groups. Alterations in the lipid profiles were also observed in the 17β-estradiol treatment groups. In contrast, SM6Met did not augment the increase in serum levels of liver injury biomarkers caused by tumor induction and no effect was observed on lipid profiles. In summary, the results from the current study demonstrate the chemopreventative effect of SM6Met on mammary tumor growth, which was comparable to that of TAM, without eliciting the negative side-effects observed with this SOC endocrine therapy. Furthermore, the results of this study also showed some responsiveness of LA7-induced tumors to estrogen and SOC endocrine therapies. Thus, this model may be useful in evaluating potential endocrine therapies for hormone responsive BC.

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Section: Introductionmentioning

confidence: 99%

Chemoprevention of LA7-Induced Mammary Tumor Growth by SM6Met, a Well-Characterized Cyclopia Extract

et al. 2018

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“…Tumors are induced in rats by a single dose of oral 7,12-dimethylbenz(a) anthracene (DMBA) or intravenous or subcutaneous N-methylnitrosurea (NMU); they form with a latency between 8 and 12 weeks and a nearly 100% incidence (Russo & Russo 1996). Both NMU and DMBA-induced tumors express ER and PR (Alvarado et al 2017). Administration of medroxyprogesterone acetate (MPA) decreases latency and increases the incidence of DMBAinduced tumors (Benakanakere et al 2006).…”

Section: Chemically Induced Rodent Models and Genetically Engineered mentioning

confidence: 99%

The challenges of modeling hormone receptor-positive breast cancer in mice

Özdemir¹,

Sflomos²,

Brisken³

2018

Endocrine-Related Cancer

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Estrogen receptor-positive (ER+) tumors account for 70-80% of all breast cancer (BC) cases and are characterized by estrogen dependency for their growth. Endocrine therapies using estrogen receptor antagonists or aromatase inhibitors represent a key component of the standard of care for these tumors. The occurrence of de novo or acquired resistance to estrogen withdrawal represents an important clinical problem, impacting on patient survival. In addition, despite an initially favorable outcome, a part of ER+ BC patients present with disease recurrence locally or at distant sites years or even decades after apparent remission. models that closely mimic human disease are urgently needed to study the biology of these tumors, investigate the molecular mechanisms underlying endocrine resistance and identify patients at risk of recurrence. Despite the similarities in the overall hormonal regulation of mammary gland development between mice and humans, the majority of the mammary carcinomas occurring in genetically engineered mouse models (GEMMs) are ER negative and most xenograft models are based on few ER+ cancer cell lines. We recently showed that the microenvironment is critical for ER+ cancer cells and discuss in this review the potential of intraductal xenograft model for basic and preclinical research.

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“…On the basis of these studies, it was suggested that the protective effect of pregnancy was partly due to modifications of the G1 or G0 phases of the cell cycle in such a way to make breast cells refractory to transformation, speculating that the prolonged resting stage of cells in G1 phase allowed for more efficient DNA repair. Later studies showed that DNA repair was more efficient in mammary epithelial cells of parous animals (compared to virgins), and DNA was less susceptible to bind DMBA, a commonly used carcinogen shown to induce tumor formation in rats and mice [ 38 , 42 , 43 ]. An interesting suggestion from these studies was that the limited proliferation capacity in parous rats was due to commitment of function in pregnancy-induced differentiation.…”

Section: Differentiation In the Mammary Gland During Pregnancy Andmentioning

confidence: 99%

“…Breast tumors in rodents possess high similarity to ERα-positive and progesterone receptor (PR)-positive human breast tumors. Thus, rodent models have been key in our understanding of breast cancer development [ 37 , 43 ]. As explained by Daniel Medina [ 50 ], there are two distinct experimental models of parity/hormone-induced protection.…”

Section: Female Hormones Pregnancy and Prevention Of Breast Cancmentioning

confidence: 99%

Good Guy or Bad Guy? The Duality of Wild-Type p53 in Hormone-Dependent Breast Cancer Origin, Treatment, and Recurrence

McGowan

Lin

Hatoum

2018

Cancers

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“Lactation is at one point perilously near becoming a cancerous process if it is at all arrested”, Beatson, 1896. Most breast cancers arise from the milk-producing cells that are characterized by aberrant cellular, molecular, and epigenetic translation. By understanding the underlying molecular disruptions leading to the origin of cancer, we might be able to design novel strategies for more efficacious treatments or, ambitiously, divert the cancerous process. It is an established reality that full-term pregnancy in a young woman provides a lifetime reduction in breast cancer risk, whereas delay in full-term pregnancy increases short-term breast cancer risk and the probability of latent breast cancer development. Hormonal activation of the p53 protein (encode by the TP53 gene) in the mammary gland at a critical time in pregnancy has been identified as one of the most important determinants of whether the mammary gland develops latent breast cancer. This review discusses what is known about the protective influence of female hormones in young parous women, with a specific focus on the opportune role of wild-type p53 reprogramming in mammary cell differentiation. The importance of p53 as a protector or perpetrator in hormone-dependent breast cancer, resistance to treatment, and recurrence is also explored.

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Prognostic factors in MNU and DMBA-induced mammary tumors in female rats

Cited by 49 publications

References 25 publications

Chemoprevention of LA7-Induced Mammary Tumor Growth by SM6Met, a Well-Characterized Cyclopia Extract

Chemoprevention of LA7-Induced Mammary Tumor Growth by SM6Met, a Well-Characterized Cyclopia Extract

The challenges of modeling hormone receptor-positive breast cancer in mice

Good Guy or Bad Guy? The Duality of Wild-Type p53 in Hormone-Dependent Breast Cancer Origin, Treatment, and Recurrence

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