Identification and transcript analysis of a novel wallaby (Macropus eugenii) basal-like breast cancer cell line

Abstract

BackgroundA 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.ResultsA 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.ConclusionThis 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.

Identification of Gene Expression Changes from Colitis to CRC in the Mouse CAC Model

“…A close relationship between cell proliferation and metabolism may occur by common regulatory pathways in cancer cells. Recently, Sharp JA et al identified new targets (including Pacsin3) for breast cancer treatment using a cDNA microarray [31]. Furthermore, Roach W et al observed that Pascin3 overexpression increases adipocyte glucose transport through GLUT1 [32], which is consistent with our data because Pacsin3 is associated with negative regulation of transport.…”

Downregulation of Ches1 and other novel genes in oral cancer cells chronically exposed to areca nut extract

“…KRT-17, an intermediate filament, was recently associated with metastatic and advanced cancers in several microarray studies. 8,26,27 RT-PCR further confirmed that KRT-17 was upregulated in the areca nut extract-trained sublines. Therefore, it is possible that areca nut extract affects cellular invasion, at least partially through the upregulation of KRT-17, thereby leading to a more malignant phenotype.…”

Stress- and Rho-activated ZO-1–associated nucleic acid binding protein binding to p21 mRNA mediates stabilization, translation, and cell survival

“…The ZONAB-dependent survival pathway thus provides a possible therapeutic opportunity to target ZONAB to induce cell death in cancer cells. This survival pathway seems up-regulated in different types of carcinomas because ZONAB has been reported to be upregulated in cancers form different tissues (14)(15)(16)(17)(18)(19)(20). Therapeutic targeting of ZONAB might also improve the effectiveness of existing therapies, because depletion enhanced cell death in response to Taxol (Fig.…”

“…ZONAB is activated in different types of cancers (14)(15)(16)(17)(18)(19)(20); hence, it would be important to know whether and how ZONAB promotes cell survival in response to cytotoxic stress and proinflammatory signals because targeting such survival pathways offers therapeutic benefits.…”