BACKGROUND: Generation of novel spontaneous ER positive mammary tumor animal 
model from heterozygous NIH nude mice.
METHODS: Using brother-sister mating with pedigree expansion system, we derived 
a colony of heterozygous breeding females showing ER-Positive tumors around the 
age of 6 months. Complete blood picture, differential leukocyte count, and serum 
levels of Estrogen, Alanine amino transferase (SGPT), Aspartate amino 
transferase (SGOT), total protein and albumin were estimated. Aspiration 
biopsies and microbiology were carried out. Gross pathology of the tumors and 
their metastatic potential were assessed. The tumors were excised and further 
characterized using histopathology, cytology, electron microscopy (EM), 
molecular markers and Mouse mammary Tumor Virus - Long Terminal Repeats (MMTV 
LTR) specific RT-PCR.
RESULTS: The tumors originated from 2nd or 5th or both the mammary glands and 
were multi-nodulated with variable central necrosis accompanied with an 
accumulation of inflammatory exudate. Significant increases in estrogen, SGPT, 
SGOT and neutrophils levels were noticed. Histopathologically, invasive nodular 
masses of pleomorphic tubular neoplastic epithelial cells invaded fibro-vascular 
stroma, adjacent dermis and subcutaneous tissue. Metastatic spread through 
hematogenous and regional lymph nodes, into liver, lungs, spleen, heart and 
dermal lymphatics was observed. EM picture revealed no viral particles and 
MMTV-negativity was confirmed through MMTV LTR-specific RT-PCR. High expression 
of ER alpha, moderate to high expression of proliferating cell nuclear antigen 
(PCNA), moderate expression of vimentin and Cytokeratin 19 (K19) and low 
expression of p53 were observed in tumor sections, when compared with that of 
the normal mammary gland.
CONCLUSION: Since 75% of human breast cancer were classified ER-positive and as 
our model mimics (in most of the characteristics, such as histopathology, 
metastasis, high estrogen levels) the ER-positive luminal epithelial-like human 
breast cancer, this model will be an attractive tool to understand the biology 
of estrogen-dependant breast cancer in women. To our knowledge, this is the 
first report of a spontaneous mammary model displaying regional lymph node 
involvement with both hematogenous and lymphatic spread to liver, lung, heart, 
spleen and lymph nodes.