Histopathological alterations during breast carcinogenesis in a rat model induced by 7,12-Dimethylbenz (a) anthracene and estrogen-progestogen combinations.

Studies have shown that the development of breast cancer (BC) is a multi-step process that occurs sequentially from normal to usual hyperplasia, atypical hyperplasia, carcinoma in situ, and finally the invasive stages of carcinoma. Our study investigated the histopathological alterations in breast tissue in a Sprague-Dawley (SD) rat model induced by 7,12-Dimethylbenz (a) anthracene (DMBA) and estrogen-progestogen (E-P). Fifty rats were randomly divided into five groups (n = 10 each) and administered the E-P/DMBA combination. After the induction of BC, breast tissue samples were obtained from the rats and stained with hematoxylin-eosin (HE). Breast tissues from 10 rats and 10 human patients were obtained for comparison. The expression of P63, CK5/6 and CK34βE12 was observed and analyzed using the SPSS 17.0 software. The HE results showed ductal epithelial hyperplasia with forming a second lumen or papillary structure, atypical hyperplasia with atypical proliferative cells, forming a cross-bridge or cribriform structure in breast tissues from the rats samples. The IHC results showed that the expression of P63 was not significantly different between rat and human breast tissue (P > 0.05), but its expression in rat and human tissue was significantly different between UDH, ADH, DCIS and IDC (P < 0.01). A similar trend was observed for the expression of CK5/6 and CK34βE12 too. Thus, the findings in this model may reflect the histopathological changes that occur during the progression of human BC. Therefore, this model could be used for the establishment of BC models to investigate the prevention and treatment of BC.

[1]  Zhigang Yu,et al.  Establishment of novel rat models for premalignant breast disease , 2014, Chinese medical journal.

[2]  P. Oliveira,et al.  Re: establishment of novel rat models for premalignant breast disease. , 2014, Chinese medical journal.

[3]  M. Morris,et al.  Chemopreventive and anti‐angiogenic effects of dietary phenethyl isothiocyanate in an N‐methyl nitrosourea‐induced breast cancer animal model , 2013, Biopharmaceutics & drug disposition.

[4]  A. Tjønneland,et al.  Serum estrogen and SHBG levels and breast cancer incidence among users and never users of hormone replacement therapy , 2012, Cancer Causes & Control.

[5]  P. Kondaiah,et al.  Gene Expression Signature of DMBA-Induced Hamster Buccal Pouch Carcinomas: Modulation by Chlorophyllin and Ellagic Acid , 2012, PloS one.

[6]  S. Manoharan,et al.  Chemopreventive potential of geraniol in 7,12-dimethylbenz(a) anthracene (DMBA) induced skin carcinogenesis in Swiss albino mice. , 2012, Journal of environmental biology.

[7]  S. Manoharan,et al.  Chemopreventive efficacy of geraniol against 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis , 2011, Redox report : communications in free radical research.

[8]  J. Stingl.  Estrogen and Progesterone in Normal Mammary Gland Development and in Cancer , 2011, Hormones & cancer.

[9]  Misty J. Williams-Fritze,et al.  Use of p63, a myoepithelial cell marker, in determining the invasiveness of spontaneous mammary neoplasia in a rhesus macaque (Macaca mulatta). , 2011, Journal of the American Association for Laboratory Animal Science : JAALAS.

[10]  E. Baracat,et al.  Breast histomorphometry of rats treated with estrogen and/or progestogen. , 2011, Revista da Associacao Medica Brasileira.

[11]  Emily S. Reisenbichler,et al.  Luminal cytokeratin expression profiles of breast papillomas and papillary carcinomas and the utility of a cytokeratin 5/p63/cytokeratin 8/18 antibody cocktail in their distinction , 2011, Modern Pathology.

[12]  S. Manoharan,et al.  Genistein and daidzein, in combination, protect cellular integrity during 7,12-dimethylbenz[a]anthracene (DMBA) induced mammary carcinogenesis in Sprague-Dawley rats. , 2011, African journal of traditional, complementary, and alternative medicines : AJTCAM.

[13]  S. Haslam,et al.  Amphiregulin Mediates Estrogen, Progesterone, and EGFR Signaling in the Normal Rat Mammary Gland and in Hormone-Dependent Rat Mammary Cancers , 2010, Hormones & cancer.

[14]  C. Besch-Williford,et al.  Synthetic Progestins Differentially Promote or Prevent 7,12-Dimethylbenz(a)anthracene–Induced Mammary Tumors in Sprague-Dawley Rats , 2010, Cancer Prevention Research.

[15]  Weiqin Jiang,et al.  Collection of Epithelial Cells from Rodent Mammary Gland Via Laser Capture Microdissection Yielding High-Quality RNA Suitable for Microarray Analysis , 2010, Biological Procedures Online.

[16]  J. Graham,et al.  DNA replication licensing and progenitor numbers are increased by progesterone in normal human breast. , 2009, Endocrinology.

[17]  Gloria Bertoli,et al.  A rat mammary gland cancer cell with stem cell properties of self-renewal and multi-lineage differentiation , 2008, Cytotechnology.

[18]  A. Masamune,et al.  Activation of Notch signaling in tumorigenesis of experimental pancreatic cancer induced by dimethylbenzanthracene in mice , 2007, Cancer science.

[19]  J. Thiery,et al.  Développement de la glande mammaire : rôle des cellules basales myoépithéliales , 2006 .

[20]  J. Thiery,et al.  [Mammary gland development: Role of basal myoepithelial cells]. , 2006, Journal de la Societe de biologie.

[21]  F. Schmitt,et al.  p63: A Novel Myoepithelial Cell Marker in Canine Mammary Tissues , 2003, Veterinary pathology.

[22]  Meenakshi Singh,et al.  A Comparison of the Histopathology of Premalignant and Malignant Mammary Gland Lesions Induced in Sexually Immature Rats with those Occurring in the Human , 2000, Laboratory Investigation.

[23]  大井 恭代.  Influence of estrogen and progesterone on the induction of mammary carcinomas by 7,12-dimethylbenz(a)anthracene in ovariectomized rats , 1992 .

[24]  J. Russo,et al.  Susceptibility of the mammary gland to carcinogenesis. III. The cell of origin of rat mammary carcinoma. , 1983, The American journal of pathology.

[25]  R. Ullrich,et al.  Detection of ductal dysplasia in mammary outgrowths derived from carcinogen-treated virgin female BALB/c mice. , 1982, Cancer research.

[26]  J. Russo,et al.  Pathogenesis of Mammary Carcinomas Induced in Rats by 7, 12-Dimethylbenz[a]anthracene , 1977 .