Pratama Dyah Ayu Oktavianie Ardhiana, Cahyati Anggun Nur, Kustiati Ulayatul, Hardian Andreas Bandang, Permata Fajar Shodiq
Laboratory of Veterinary Pathology, Faculty of Veterinary Medicine, Universitas Brawijaya, Malang, East Java, 65143, Indonesia.
Study Program of Veterinary Medicine, Faculty of Veterinary Medicine, Universitas Brawijaya, Malang, East Java, 65143, Indonesia.
F1000Res. 2024 Aug 5;12:606. doi: 10.12688/f1000research.132524.1. eCollection 2023.
Mammary cancer, called breast cancer in humans, results from the abnormal growth of cells in the mammary glands that attack the surrounding tissue. The process of carcinogenesis at the molecular level can be monitored through the production of proteins as biomarkers for carcinogenesis. 7,12-Dimethylbenz[a]anthracene (DMBA) is a known carcinogenic compound. This study aimed to analyze the proteomic profile as critical data regarding DMBA-induced carcinogenesis in Sprague‒Dawley rats. Experimental animals were divided into two groups: a treatment group given DMBA at a dose of 10 mg/kg (intramammary) at intervals of 48 hours for a total of 10 doses, and a negative control group that was not given any treatment. Measurement of the total protein concentration was carried out using a spectrophotometer, and the data were analyzed using a t-test, while the characterization of protein profiles was carried out based on molecular weight data using SDS‒PAGE. Mammary gland histopathology was evaluated by hematoxylin and eosin (H&E) staining. The results showed a significant (p<0.05) increase of 27% in the total protein concentration in the rat mammary cancer model. The results of proteomic characterization showed a protein profile containing proteins of 187, 169, 68, 64, 53, 41, 24, 18, and 14 kDa, which were suspected to be HER-2, Nischarin, COX-2, Albumine, Vimentin, ACTB, TNF, p16, and fatty acid binding protein 3 (FABP3), respectively. Histopathology of the mammary glands showed an irregular and indistinct arrangement of the alveoli and extensive epithelial cell proliferation from the surface to the lumen of the mammary ducts, and the mammary stroma showed the formation of new epithelial cells, which were cancer cells that spread to surrounding tissue. The proteomic profile was strongly associated with morphological alterations in mammary carcinogenesis in a rat model of DMBA-induced mammary cancer.
乳腺癌,在人类中称为乳癌,是由乳腺中细胞异常生长并侵袭周围组织所致。致癌作用在分子水平的过程可通过作为致癌生物标志物的蛋白质产生来监测。7,12-二甲基苯并[a]蒽(DMBA)是一种已知的致癌化合物。本研究旨在分析蛋白质组学图谱,作为关于DMBA诱导的Sprague-Dawley大鼠致癌作用的关键数据。实验动物分为两组:治疗组以10mg/kg的剂量(经乳腺内)每隔48小时给予DMBA,共给药10次;阴性对照组未接受任何治疗。使用分光光度计测量总蛋白浓度,并使用t检验分析数据,而蛋白质图谱的表征则基于使用SDS-PAGE的分子量数据进行。通过苏木精和伊红(H&E)染色评估乳腺组织病理学。结果显示,大鼠乳腺癌模型中总蛋白浓度显著(p<0.05)增加了27%。蛋白质组学表征结果显示,蛋白质图谱包含分子量为187、169、68、64、53、41、24、18和14kDa的蛋白质,分别疑似为HER-2、Nischarin、COX-2、白蛋白、波形蛋白、肌动蛋白、肿瘤坏死因子、p16和脂肪酸结合蛋白3(FABP3)。乳腺组织病理学显示,肺泡排列不规则且不清晰,乳腺导管从表面到管腔有广泛的上皮细胞增殖,乳腺间质显示有新上皮细胞形成,这些新上皮细胞即为扩散至周围组织的癌细胞。在DMBA诱导的大鼠乳腺癌模型中,蛋白质组学图谱与乳腺致癌过程中的形态学改变密切相关。