Establishment of a mammary carcinoma cell line from Syrian hamsters treated with N-methyl-N-nitrosourea

Malari A. Coburn, Sabrina Brueggemann, Shilpa Bhatia, Bing Cheng, Benjamin D.L. Li, Xiao Lin Li, Natalia Luraguiz, Yulia Y. Maxuitenko, Elysse A. Orchard, Songlin Zhang, Mariam A. Stoff-Khalili, James Michael Mathis, Heather E. Kleiner-Hancock

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)82-90
Number of pages9
JournalCancer Letters
Volume312
Issue number1
DOIs
StatePublished - 15 Dec 2011

Fingerprint

Methylnitrosourea
Mesocricetus
Breast Neoplasms
Cell Line
Cricetinae
Estrogen Receptors
Tamoxifen
Neoplasms
Adenocarcinoma
Breast
Keratin-6
Keratin-5
Incidence
Aneuploidy
Tumor Cell Line
Carcinogens
Agar
Chromosomes
Cell Proliferation
Therapeutics

Keywords

  • Adenocarcinoma
  • Breast cancer
  • HMAM5 cell line
  • MNU
  • Mammary tumor
  • N-methyl-N-nitrosourea
  • Syrian hamster

Cite this

Coburn, M. A., Brueggemann, S., Bhatia, S., Cheng, B., Li, B. D. L., Li, X. L., ... Kleiner-Hancock, H. E. (2011). Establishment of a mammary carcinoma cell line from Syrian hamsters treated with N-methyl-N-nitrosourea. Cancer Letters, 312(1), 82-90. https://doi.org/10.1016/j.canlet.2011.08.003
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, James Michael ; Kleiner-Hancock, Heather E. / Establishment of a mammary carcinoma cell line from Syrian hamsters treated with N-methyl-N-nitrosourea. In: Cancer Letters. 2011 ; Vol. 312, No. 1. pp. 82-90.
@article{76b7553fcbd34c6f8a71dad87655e6d3,
title = "Establishment of a mammary carcinoma cell line from Syrian hamsters treated with N-methyl-N-nitrosourea",
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 = "Adenocarcinoma, Breast cancer, HMAM5 cell line, MNU, Mammary tumor, N-methyl-N-nitrosourea, Syrian hamster",
author = "Coburn, {Malari A.} and Sabrina Brueggemann and Shilpa Bhatia and Bing Cheng and Li, {Benjamin D.L.} and Li, {Xiao Lin} and Natalia Luraguiz and Maxuitenko, {Yulia Y.} and Orchard, {Elysse A.} and Songlin Zhang and Stoff-Khalili, {Mariam A.} and Mathis, {James Michael} and Kleiner-Hancock, {Heather E.}",
year = "2011",
month = "12",
day = "15",
doi = "10.1016/j.canlet.2011.08.003",
language = "English",
volume = "312",
pages = "82--90",
journal = "Cancer Letters",
issn = "0304-3835",
publisher = "Elsevier Ireland Ltd",
number = "1",

}

Coburn, MA, Brueggemann, S, Bhatia, S, Cheng, B, Li, BDL, Li, XL, Luraguiz, N, Maxuitenko, YY, Orchard, EA, Zhang, S, Stoff-Khalili, MA, Mathis, JM & Kleiner-Hancock, HE 2011, 'Establishment of a mammary carcinoma cell line from Syrian hamsters treated with N-methyl-N-nitrosourea', Cancer Letters, vol. 312, no. 1, pp. 82-90. https://doi.org/10.1016/j.canlet.2011.08.003

Establishment of a mammary carcinoma cell line from Syrian hamsters treated with N-methyl-N-nitrosourea. / 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, James Michael; Kleiner-Hancock, Heather E.

In: Cancer Letters, Vol. 312, No. 1, 15.12.2011, p. 82-90.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Establishment of a mammary carcinoma cell line from Syrian hamsters treated with N-methyl-N-nitrosourea

AU - Coburn, Malari A.

AU - Brueggemann, Sabrina

AU - Bhatia, Shilpa

AU - Cheng, Bing

AU - Li, Benjamin D.L.

AU - Li, Xiao Lin

AU - Luraguiz, Natalia

AU - Maxuitenko, Yulia Y.

AU - Orchard, Elysse A.

AU - Zhang, Songlin

AU - Stoff-Khalili, Mariam A.

AU - Mathis, James Michael

AU - Kleiner-Hancock, Heather E.

PY - 2011/12/15

Y1 - 2011/12/15

N2 - 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.

AB - 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.

KW - Adenocarcinoma

KW - Breast cancer

KW - HMAM5 cell line

KW - MNU

KW - Mammary tumor

KW - N-methyl-N-nitrosourea

KW - Syrian hamster

UR - http://www.scopus.com/inward/record.url?scp=80053326150&partnerID=8YFLogxK

U2 - 10.1016/j.canlet.2011.08.003

DO - 10.1016/j.canlet.2011.08.003

M3 - Article

VL - 312

SP - 82

EP - 90

JO - Cancer Letters

JF - Cancer Letters

SN - 0304-3835

IS - 1

ER -