Congenic rats with higher arylamine N-acetyltransferase 2 activity exhibit greater carcinogen-induced mammary tumor susceptibility independent of carcinogen metabolism

Stepp, Marcus W.; Doll, Mark A.; Samuelson, David J.; Sanders, Mary Ann; States, J. Christopher; Hein, David W.

doi:10.1186/s12885-017-3221-9

Cited by 18 publications

(16 citation statements)

References 48 publications

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“…Recent meta-analyses suggest the associations of NAT1 genetic polymorphisms with pancreatic (Zhang et al, 2015) and urinary bladder (Dhaini et al, 2017) cancers. Congenic rats with higher arylamine N-acetyltransferase 2 activity (homologous to human NAT1) exhibit greater carcinogen-induced mammary tumor susceptibility (Stepp et al, 2017). Overexpression of NAT1 enhances breast cancer cell proliferation and was associated with a gene signature of epithelial-tomesenchymal transition in breast tumors (Adam et al, 2003;Savci-Heijink et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

High N-Acetyltransferase 1 Expression is Associated with Estrogen Receptor Expression in Breast Tumors, but is not Under Direct Regulation by Estradiol, 5α-androstane-3β, 17β-Diol, or Dihydrotestosterone in Breast Cancer Cells

Zhang

Carlisle

Doll

et al. 2018

J Pharmacol Exp Ther

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N-acetyltransferase 1 (NAT1) is an enzyme that metabolizes carcinogens, which suggests a potential role in breast carcinogenesis. High expression in breast tumors is associated with estrogen receptor (ER+) and the luminal subtype. We report that mRNA transcript, protein, and enzyme activity were higher in human breast tumors with high expression of ER/ compared with normal breast tissue. There was a strong correlation between promoter and NAT1 protein expression/enzyme activity. High expression in tumors was not the result of adipocytes, as evidenced by low perilipin ( expression. ,, and expression were associated in tumor biopsies. Direct regulation of transcription by estradiol (E) was investigated in ER (+) MCF-7 and T47D breast cancer cells. E did not increase transcript expression but increased progesterone receptor expression in a dose-dependent manner. Likewise, transcript levels were not increased by dihydrotestosterone (DHT) or 5-androstane-3, (3-adiol) 17-diol. Dithiothreitol increased levels of the activated, spliced in ER (+) MCF-7 and T47D breast cancer cells but did not affect or expression. We conclude that expression is not directly regulated by E, DHT, 3-adiol, or dithiothreitol despite high and expression in luminal A breast cancer cells, suggesting that , and expression may share a common transcriptional network arising from the luminal epithelium associated with better survival in breast cancer. Clusters of high-expression genes, including in breast tumors might serve as potential targets for novel therapeutic drug development.

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Section: Introductionmentioning

confidence: 99%

High N-Acetyltransferase 1 Expression is Associated with Estrogen Receptor Expression in Breast Tumors, but is not Under Direct Regulation by Estradiol, 5α-androstane-3β, 17β-Diol, or Dihydrotestosterone in Breast Cancer Cells

Zhang

Carlisle

Doll

et al. 2018

J Pharmacol Exp Ther

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“…Although this finding is consistent with AcCoA hydrolysis catalyzed by NAT1, it does not provide evidence this is the primary or sole mechanism for the elevation of AcCoA. Rat embryonic fibroblasts from rapid acetylator congenic rats have lower levels of AcCoA than rat embryonic fibroblasts derived from slow acetylator congenic rats [65]. Thus while a direct connection for physiological differences in AcCoA levels cannot be drawn to NAT1 AcCoA hydrolysis, accumulating data suggest that NAT1 may influence endogenous AcCoA levels.…”

Section: Effects Of Small Molecule Nat1 Inhibitor On Mda-mb-231 Breasmentioning

confidence: 61%

Role of human arylamine n-acetyltransferase 1 in tumorigenesis and cancer biology.

Stepp¹

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help of Dr. Mary Ann Sanders, in teaching me pathology classifications and helping classify the pathology slides. Thank you to Dr. Dennis Warner for instructing me on the isolation and culture of mouse embryonic fibroblasts. Thank you to Jamie Rush for being a helpful neighbor in the laboratory. Thank you to the summer students that I had the pleasure of instructing over the summers of my graduate studies.

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“…Penelitian lain juga melaporkan bahwa tikus yang mendapat perlakuan sonde 65mg/kgBB DMBA mengalami peningkatan lebih rendah dibanding yang tidak mendapat induksi DMBA. 15 Penelitian lain juga melaporkan bahwa induksi DMBA tidak menyebabkan perubahan bermakna pada berat badan hewan coba, diantaranya dilaporkan oleh Al-Saeedi 12 yang melaporkan bahwa tidak terjadi perbedaan secara bermakna pada berat badan tikus Sprague-Dawley normal dan yang mendapat induksi DMBA 10 mg/ekor melalui sonde dan diamati tiga minggu sekali selama 12 minggu, namun setelah 12 minggu tikus DMBA+ mengalami penurunan berat badan 5-6% sedang tikus DMBA-mengalami peningkatan berat badan 5-7%. Pada penelitian ini peningkatan berat badan tikus DMBA+ lebih rendah daripada tikus DMBA-dimungkinkan karena tikus DMBA+ mengalami penurunan nafsu makan yang terjadi sejak minggu ke-4 setelah induksi DMBA yang ditandai dengan adanya sisa pakan setiap harinya.…”

Section: Pembahasanunclassified

Ekstrak Propolis Memperbaiki Profil Berat Badan Tikus Model Kanker Payudara yang Diinduksi dengan 7,12-dymethyilbenz(a) antracene (DMBA)

Kusnul¹,

Suryono²,

Tamsuri³

2019

mpk

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Body weight is a general indicator for assessing health status. Various diseases cause drastic weight loss, including cancer. Propolis is a bee product that has various therapeutic effects such as; anti-bacterial, antitumor, antioxidant and immunomodulatory. Propolis is also reported to be able to reduce digestive organ disorders, increase appetite and improve metabolic processes. Chemicals such as 7.12-dymethyilbenz (a) antracene (DMBA) are widely reported to have strong carcinogenic effects, especially in Sprague–Dawley rat. This study aims to assess the effect of propolis extract on the weight of Sprague–Dawley female rat induced with DMBA (7,12-dymethylbenz (a) antracene). Twenty-four female Sprague–Dawley rats 45-50 days old were induced by DMBA with a combination of injection and oral methods, as negative controls 6 Sprague–Dawley rats without DMBA induction. At the 11th week randomized negative control rats and DMBA treated rats were taken for histopathological examination of breast tissue. After it was found that rat with DMBA treatment were positive for breast cancer, in the 12th week the rat that had received DMBA treatment were divided into 4 groups, 3 groups received oral propolis extract through a gastric sonde with doses 50, 100 and 200 mg in 1 ml of corn oil, 1 group as a positive control did not get the treatment of propolis extract. Body weight is weighed before starting treatment and monitored every two weeks to 15 weeks. The results of weighing showed that the group of rat that received DMBA increased their body weight lower than the group without DMBA, and then the treatment group of propolis extract increased their body weight higher than the group without the treatment of propolis extract. The results showed that the treatment of propolis extract had a potency to improve the body weight profile of rat breast cancer model induced by DMBA. Abstrak Berat badan merupakan indikator umum untuk menilai status kesehatan. Berbagai penyakit menyebabkan penurunan berat badan yang drastis, diantaranya adalah kanker. Propolis merupakan produk lebah yang memiliki berbagai efek terapi seperti; anti bakteri, anti tumor, antioksidan dan imunomodulator. Propolis juga dilaporkan mampu menurunkan gangguan organ pencernaan, peningkatan nafsu makan, dan perbaikan proses metabolisme. Bahan kimia seperti 7,12-dymethyilbenz(a)antracene (DMBA) banyak dilaporkan memiliki efek karsinogenik yang kuat khususnya terhadap tikus Sprague–Dawley. Penelitian ini bertujuan untuk menilai pengaruh pemberian ekstrak propolis terhadap berat badan tikus Sprague–Dawley betina yang diinduksi untuk mengalami kanker payudara dengan DMBA. Sebanyak 24 ekor tikus Sprague– Dawley betina berumur 45-50 hari diinduksi dengan DMBA dengan kombinasi metode injeksi dan oral, sebagai kontrol negatif 6 ekor tikus Sprague–Dawley tanpa induksi DMBA. Pada minggu ke-11 diambil secara acak tikus kontrol negatif dan tikus perlakuan DMBA untuk dilakukan pemeriksaan histolopatogi jaringan payudara. Setelah didapatkan bahwa tikus dengan perlakuan DMBA positif mengalami kanker payudara, pada minggu ke-12 tikus yang telah mendapat perlakuan DMBA dibagi menjadi 4 kelompok, 3 kelompok mendapat ekstrak propolis oral melalui sonde dengan dosis masing-masing 50, 100, dan 200 mg dalam 1 ml minyak jagung, 1 kelompok sebagai kontrol positif tidak mendapat perlakuan ekstrak propolis. Berat badan ditimbang sebelum mulai perlakuan dan dipantau tiap dua minggu sampai 15 minggu. Hasil penimbangan berat badan menunjukkan bahwa kelompok tikus yang mendapat DMBA peningkatan berat badannya lebih rendah dibanding kelompok tanpa DMBA, dan selanjutnya kelompok perlakuan ekstrak propolis kenaikan berat badannya lebih tinggi dibanding kelompok tanpa perlakuan ekstrak propolis. Hasil penelitian menunjukkan bahwa perlakuan ekstrak propolis memiliki potensi memperbaiki profil berat badan tikus model kanker payudara yang diinduksi dengan DMBA.

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Congenic rats with higher arylamine N-acetyltransferase 2 activity exhibit greater carcinogen-induced mammary tumor susceptibility independent of carcinogen metabolism

Cited by 18 publications

References 48 publications

High N-Acetyltransferase 1 Expression is Associated with Estrogen Receptor Expression in Breast Tumors, but is not Under Direct Regulation by Estradiol, 5α-androstane-3β, 17β-Diol, or Dihydrotestosterone in Breast Cancer Cells

High N-Acetyltransferase 1 Expression is Associated with Estrogen Receptor Expression in Breast Tumors, but is not Under Direct Regulation by Estradiol, 5α-androstane-3β, 17β-Diol, or Dihydrotestosterone in Breast Cancer Cells

Role of human arylamine n-acetyltransferase 1 in tumorigenesis and cancer biology.

Ekstrak Propolis Memperbaiki Profil Berat Badan Tikus Model Kanker Payudara yang Diinduksi dengan 7,12-dymethyilbenz(a) antracene (DMBA)

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