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Hormone-induced protection of mammary tumorigenesis in genetically engineered mouse models.

Rajkumar L, Kittrell FS, Guzman RC, Brown PH, Nandi S, Medina D - Breast Cancer Res. (2007)

Bottom Line: In the p53- mammary transplant model, a 2-week exposure to estrogen and progesterone during the immediate post-pubertal stage (2 to 4 weeks after transplantation) of mammary development decreased mammary tumorigenesis by 70 to 88%.One possible mechanism for the decrease in mammary tumorigenesis may be an altered proliferation activity as the bromodeoxyuridine labeling index was decreased by 85% in the mammary glands of hormone-treated mice.Because these experiments were performed in model systems that mimic many essential elements of human breast cancer, the results strengthen the rationale for translating this prevention strategy to humans at high risk for developing breast cancer.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, Texas Tech University Health Sciences Center, 4800 Alberta Avenue, El Paso, TX 79905, USA.

ABSTRACT

Introduction: The experiments reported here address the question of whether a short-term hormone treatment can prevent mammary tumorigenesis in two different genetically engineered mouse models.

Methods: Two mouse models, the p53- mammary epithelial transplant and the c-neu mouse, were exposed to estrogen and progesterone for 2 and 3 weeks, respectively, and followed for development of mammary tumors.

Results: In the p53- mammary transplant model, a 2-week exposure to estrogen and progesterone during the immediate post-pubertal stage (2 to 4 weeks after transplantation) of mammary development decreased mammary tumorigenesis by 70 to 88%. At 45 weeks after transplantation, analysis of whole mounts of the mammary outgrowths demonstrated the presence of premalignant hyperplasias in both control and hormone-treated glands, indicating that the hormone treatment strongly affects the rate of premalignant progression. One possible mechanism for the decrease in mammary tumorigenesis may be an altered proliferation activity as the bromodeoxyuridine labeling index was decreased by 85% in the mammary glands of hormone-treated mice. The same short-term exposure administered to mature mice at a time of premalignant development also decreased mammary tumorigenesis by 60%. A role for stroma and/or systemic mediated changes induced by the short-term hormone (estrogen/progesterone) treatment was demonstrated by an experiment in which the p53- mammary epithelial cells were transplanted into the cleared mammary fat pads of previously treated mice. In such mice, the tumor-producing capabilities of the mammary cells were also decreased by 60% compared with the same cells transplanted into unexposed mice. In the second set of experiments using the activated Her-2/neu transgenic mouse model, short-term estradiol or estradiol plus progesterone treatment decreased mammary tumor incidence by 67% and 63%, and tumor multiplicity by 91% and 88%, respectively. The growth rate of tumors arising in the hormone-treated activated Her-2/neu mice was significantly lower than tumors arising in non-hormone treated mice.

Conclusion: Because these experiments were performed in model systems that mimic many essential elements of human breast cancer, the results strengthen the rationale for translating this prevention strategy to humans at high risk for developing breast cancer.

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Effect of short-term hormone treatment on mammary cancer multiplicity in the activated Her-2/neu transgenic mice. The group of mice (n = 21) treated with estradiol alone developed a total of 13 mammary tumors and the group of mice (n = 24) treated with estradiol plus progesterone developed a total of 20 mammary tumors by 8 to 9 months of age; in comparison, the group of control mice (n = 20) developed a total of 136 mammary tumors (p < 0.005). Results are expressed as means ± SEM.
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Figure 8: Effect of short-term hormone treatment on mammary cancer multiplicity in the activated Her-2/neu transgenic mice. The group of mice (n = 21) treated with estradiol alone developed a total of 13 mammary tumors and the group of mice (n = 24) treated with estradiol plus progesterone developed a total of 20 mammary tumors by 8 to 9 months of age; in comparison, the group of control mice (n = 20) developed a total of 136 mammary tumors (p < 0.005). Results are expressed as means ± SEM.

Mentions: All the control mice developed mammary cancers by 5 months of host age with a multiplicity of 6.8 cancers per mouse. Treatment with estradiol (0.6 cancers per mouse) or estradiol plus progesterone (0.8 cancers per mouse) drastically reduced mammary cancer multiplicity and also approximately doubled the mammary cancer latency (Figures 8 and 9). This experiment was repeated once with identical results. A second repeat experiment was not informative because the control untreated mice did not develop tumors with their usual early latency of 13 to 15 weeks of host age but started to develop tumors only at 30 weeks.


Hormone-induced protection of mammary tumorigenesis in genetically engineered mouse models.

Rajkumar L, Kittrell FS, Guzman RC, Brown PH, Nandi S, Medina D - Breast Cancer Res. (2007)

Effect of short-term hormone treatment on mammary cancer multiplicity in the activated Her-2/neu transgenic mice. The group of mice (n = 21) treated with estradiol alone developed a total of 13 mammary tumors and the group of mice (n = 24) treated with estradiol plus progesterone developed a total of 20 mammary tumors by 8 to 9 months of age; in comparison, the group of control mice (n = 20) developed a total of 136 mammary tumors (p < 0.005). Results are expressed as means ± SEM.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1851398&req=5

Figure 8: Effect of short-term hormone treatment on mammary cancer multiplicity in the activated Her-2/neu transgenic mice. The group of mice (n = 21) treated with estradiol alone developed a total of 13 mammary tumors and the group of mice (n = 24) treated with estradiol plus progesterone developed a total of 20 mammary tumors by 8 to 9 months of age; in comparison, the group of control mice (n = 20) developed a total of 136 mammary tumors (p < 0.005). Results are expressed as means ± SEM.
Mentions: All the control mice developed mammary cancers by 5 months of host age with a multiplicity of 6.8 cancers per mouse. Treatment with estradiol (0.6 cancers per mouse) or estradiol plus progesterone (0.8 cancers per mouse) drastically reduced mammary cancer multiplicity and also approximately doubled the mammary cancer latency (Figures 8 and 9). This experiment was repeated once with identical results. A second repeat experiment was not informative because the control untreated mice did not develop tumors with their usual early latency of 13 to 15 weeks of host age but started to develop tumors only at 30 weeks.

Bottom Line: In the p53- mammary transplant model, a 2-week exposure to estrogen and progesterone during the immediate post-pubertal stage (2 to 4 weeks after transplantation) of mammary development decreased mammary tumorigenesis by 70 to 88%.One possible mechanism for the decrease in mammary tumorigenesis may be an altered proliferation activity as the bromodeoxyuridine labeling index was decreased by 85% in the mammary glands of hormone-treated mice.Because these experiments were performed in model systems that mimic many essential elements of human breast cancer, the results strengthen the rationale for translating this prevention strategy to humans at high risk for developing breast cancer.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, Texas Tech University Health Sciences Center, 4800 Alberta Avenue, El Paso, TX 79905, USA.

ABSTRACT

Introduction: The experiments reported here address the question of whether a short-term hormone treatment can prevent mammary tumorigenesis in two different genetically engineered mouse models.

Methods: Two mouse models, the p53- mammary epithelial transplant and the c-neu mouse, were exposed to estrogen and progesterone for 2 and 3 weeks, respectively, and followed for development of mammary tumors.

Results: In the p53- mammary transplant model, a 2-week exposure to estrogen and progesterone during the immediate post-pubertal stage (2 to 4 weeks after transplantation) of mammary development decreased mammary tumorigenesis by 70 to 88%. At 45 weeks after transplantation, analysis of whole mounts of the mammary outgrowths demonstrated the presence of premalignant hyperplasias in both control and hormone-treated glands, indicating that the hormone treatment strongly affects the rate of premalignant progression. One possible mechanism for the decrease in mammary tumorigenesis may be an altered proliferation activity as the bromodeoxyuridine labeling index was decreased by 85% in the mammary glands of hormone-treated mice. The same short-term exposure administered to mature mice at a time of premalignant development also decreased mammary tumorigenesis by 60%. A role for stroma and/or systemic mediated changes induced by the short-term hormone (estrogen/progesterone) treatment was demonstrated by an experiment in which the p53- mammary epithelial cells were transplanted into the cleared mammary fat pads of previously treated mice. In such mice, the tumor-producing capabilities of the mammary cells were also decreased by 60% compared with the same cells transplanted into unexposed mice. In the second set of experiments using the activated Her-2/neu transgenic mouse model, short-term estradiol or estradiol plus progesterone treatment decreased mammary tumor incidence by 67% and 63%, and tumor multiplicity by 91% and 88%, respectively. The growth rate of tumors arising in the hormone-treated activated Her-2/neu mice was significantly lower than tumors arising in non-hormone treated mice.

Conclusion: Because these experiments were performed in model systems that mimic many essential elements of human breast cancer, the results strengthen the rationale for translating this prevention strategy to humans at high risk for developing breast cancer.

Show MeSH
Related in: MedlinePlus