Identification and transcript analysis of a novel wallaby (Macropus eugenii) basal-like breast cancer cell line.
BACKGROUND
A wide variety of animal models have been used to study human breast cancer. Murine, feline and canine mammary tumor cell lines have been studied for several decades and have been shown to have numerous aspects in common with human breast cancer. It is clear that new comparative approaches to study cancer etiology are likely to be productive.


RESULTS
A continuous line of breast carcinoma cells (WalBC) was established from a primary breast cancer that spontaneously arose in a female tammar wallaby (Macropus eugenii). The primary tumor was 1.5 cm3 and although large, did not appear to invade the stroma and lacked vimentin expression. The WalBC cell line was cultured from the primary tumor and passaged for 22 months. WalBC cells displayed an epithelial morphology when grown on plastic, were not EGF responsive, stained strongly for cyto-keratin and negatively for vimentin. WalBC cells were shown to be non-invasive within a Matrigel invasion assay and failed to produce tumors following transplantation into nude mice. Gene expression profiling of WalBC cells was performed using a cDNA microarray of nearly 10,000 mammary gland cDNA clones and compared to normal primary mammary cells and profiles of human breast cancer. Seventy-six genes were down-regulated and sixty-six genes were up-regulated in WalBC cells when compared to primary mammary cells. WalBC cells exhibited expression of known markers of basal invasive human breast cancers as well as increased KRT17, KRT 14 and KRT 19, DSP, s100A4, NDRG-1, ANXA1, TK1 and AQP3 gene expression and decreased gene expression of TIMP3, VIM and TAGLN. New targets for breast cancer treatment were identified such as ZONAB, PACSIN3, MRP8 and SUMO1 which have human homologues.


CONCLUSIONS
This study demonstrates how novel models of breast cancer can provide new fundamental clues regarding cancer etiology which may lead to new human treatments and therapies.
Sharp
Julie A
JA
CRC for Innovative Dairy Products, Department of Zoology, University of Melbourne, VIC 3010, Australia. jasharp@unimelb.edu.au
Mailer
Sonia L
SL
Thomson
Peter C
PC
Lefèvre
Christophe
C
Nicholas
Kevin R
KR
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006801:Humans; D007614:Macropodidae / Q000235:genetics*; D015674:Mammary Neoplasms, Animal / Q000235:genetics* / Q000473:pathology*; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics*; D015854:Up-Regulation
D012333:RNA, Messenger; D012334:RNA, Neoplasm