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Establishment of a mammary carcinoma cell line from Syrian hamsters treated with N-methyl-N-nitrosourea |
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| Authors: | Coburn Malari A Brueggemann Sabrina Bhatia Shilpa Cheng Bing Li Benjamin D L Li Xiao-Lin Luraguiz Natalia Maxuitenko Yulia Y Orchard Elysse A Zhang Songlin Stoff-Khalili Mariam A Mathis J Michael Kleiner-Hancock Heather E |
| Affiliation: | a Department of Pharmacology, Toxicology, and Neuroscience, LSU Health Sciences Center, Shreveport, LA 71130, USA b Department of Pathology, LSU Health Sciences Center, Shreveport, LA 71130, USA c Department of Cellular Biology and Anatomy, LSU Health Sciences Center, Shreveport, LA 71130, USA d Department of Animal Resources, LSU Health Sciences Center, Shreveport, LA 71130, USA e Department of Surgery, LSU Health Sciences Center, Shreveport, LA 71130, USA f The Gene Therapy Program, LSU Health Sciences Center, Shreveport, LA 71130, USA g The Feist-Weiller Cancer Center, Breast Cancer Focus Group, LSU Health Sciences Center, Shreveport, LA 71130, USA h Institute of Virology, University of Cologne, Fürst-Pückler-Str. 53, 50935 Cologne, Germany i Southern Research Institute, 2000 Ninth Avenue South, Birmingham, AL 35205, USA |
| Abstract: | 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. |
| Keywords: | MNU, N-methyl-N-nitrosourea DMBA, 7,12-dimethylbenz[a]anthracene DES, diethyl-stilbestrol BOP, N-nitrosobis(2-oxopropyl)amine IACUC, Institutional Animal Care and Use Committee i.p., intraperitoneal PET, Positron Emission Tomography 18F-FDG, 2-deoxy-2-[18F]fluoro- smallcaps" >d-g1ucose LSO, lutetium oxyorthosilicate crystal DMEM, Dulbecco&rsquo s Modified Essential Medium FBS, fetal bovine serum s.c., subcutaneous ADH, atypical ductal hyperplasia DCIS, ductal carcinoma in situ MGMT, O6-methylguanine-DNA methyltransferase |
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