Clearly new breast cancer models are necessary in developing novel therapies. To address this challenge, we examined mammary tumor formation in the Syrian hamster using the chemical carcinogen N-methyl-N-nitrosourea (MNU). A single 50 mg/kg intraperitoneal dose of MNU resulted in a 60% incidence of premalignant mammary lesions, and a 20% incidence of mammary adenocarcinomas. Two cell lines, HMAM4A and HMAM4B, were derived from one of the primary mammary tumors induced by MNU. The morphology of the primary tumor was similar to a high-grade poorly differentiated adenocarcinoma in human breast cancer. The primary tumor stained positively for both HER-2/neu and pancytokeratin, and negatively for both cytokeratin 5/6 and p63. When the HMAM4B cell line was implanted subcutaneously into syngeneic female hamsters, tumors grew at a take rate of 50%. A tumor derived from HMAM4B cells implanted into a syngeneic hamster was further propagated in vitro as a stable cell line HMAM5. The HMAM5 cells grew in female syngeneic hamsters with a 70% take rate of tumor formation. These cells proliferate in vitro, form colonies in soft agar, and are aneuploid with a modal chromosomal number of 74 (the normal chromosome number for Syrian hamster is 44). To determine responsiveness to the estrogen receptor (ER), a cell proliferation assay was examined using increasing concentrations of tamoxifen. Both HMAM5 and human MCF-7 (ER positive) cells showed a similar decrease at 24 h. However, MDA-MB-231 (ER negative) cells were relatively insensitive to any decrease in proliferation from tamoxifen treatment. These results suggest that the HMAM5 cell line was likely derived from a luminal B subtype of mammary tumor. These results also represent characterization of the first mammary tumor cell line available from the Syrian hamster. The HMAM5 cell line is likely to be useful as an immunocompetent model for human breast cancer in developing novel therapies.

The purpose of the current study was to determine whether a tropical ginger derived compound 1’-acetoxychavicol acetate (ACA), suppresses skin tumor promotion in K5.Stat3C mice. In a two-week study in which wild-type (WT) and K5.Stat3C mice were co-treated with either vehicle, ACA, galanga extract, or fluocinolone acetonide (FA) and tetradecanoyl phorbol acetate (TPA), only the galanga extract and FA suppressed TPA-induced skin hyperproliferation and wet weight. None of these agents were effective at suppressing p-Tyr705Stat3 expression. However, ACA and FA showed promising inhibitory effects against skin tumorigenesis in K5.Stat3C mice. ACA also suppressed phospho-p65 NF-κB activation, suggesting a potential mechanism for its action.

Two models of breast cancer to study oncolytic virotherapy were investigated in female Syrian golden hamsters. In contrast to most other species examined, the Syrian hamster is permissive for human Adenovirus replication. Single doses of 2 carcinogens to 2 different groups of animals were administered: 7,12‐dimethylbenz[a]anthracene (DMBA) or N‐methylnitrosourea (MNU). Body weights, palpations and PET imaging for tumors were recorded. Animals were necropsied and tissues were taken for primary culture, histology and H&E staining. After cell lines were established from primary tumors, karyotyping, infectivity, oncolytic activity, and growth rate were determined. Both lines contain 74 chromosomes where normal for hamster is 44. Histology determined the DMBA line was derived from a highly aggressive, poorly differentiated carcinoma. When injected into nude mice xenografts, the DMBA derived line grew rapidly, invaded into underlying muscle, and metastasized to lung and bone. The MNU line, clearly an adenocarcinoma, was syngeneicly transplanted into recipient hamsters with a take rate of <50%; those tumors were harvested, grown in primary culture, and transplanted again with a take rate of 100%. The MNU line shows promising results for use in oncolytic virotherapy while the DMBA might prove to be useful in testing for failed drugs. Funding: Feist‐Weiller Cancer Center and the LA Gene Therapy Consortium