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Recombinant Human Granulocyte Colony-Stimulating Factor Promotes Preinvasive and Invasive Estrogen Receptor-Positive Tumor Development in MMTV-erbB2 Mice.

Zhao CL, Zhang GP, Xiao ZZ, Ma ZK, Lei CP, Song SY, Feng YY, Zhao YC, Feng XS - J Breast Cancer (2015)

Bottom Line: Cellular and molecular mechanisms of G-CSF action in mammary glands were investigated via immunohistochemistry and reverse transcription polymerase chain reaction.The cancer prevention effect was associated with reduced expression of proliferating cell nuclear antigen, cluster of differentiation 34, and signal transducers and activators of transcription 3 in mammary glands by >80%.We found that G-CSF was regulated by rhG-CSF both in vitro and in vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Cancer Institute, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China.

ABSTRACT

Purpose: We investigated whether recombinant human granulocyte colony-stimulating factor (rhG-CSF) could promote the development of preinvasive and invasive breast cancer in mouse mammary tumor virus (MMTV-erbB2) mice with estrogen receptor-positive tumors.

Methods: MMTV-erbB2 mice were randomly divided into three experimental groups with 20 mice in each group. MMTV-erbB2 mice were treated with daily subcutaneous injections of vehicle or rhG-CSF (low-rhG-CSF group, rhG-CSF 0.125 µg; vehicle-rhG-CSF group, normal saline 0.25 µg; and high-rhG-CSF group, rhG-CSF 0.25 µg) at 3 months of age. Cellular and molecular mechanisms of G-CSF action in mammary glands were investigated via immunohistochemistry and reverse transcription polymerase chain reaction.

Results: Low, but not high, rhG-CSF doses significantly accelerated mammary tumorigenesis in MMTV-erbB2 mice. Short-term treatment with rhG-CSF could significantly promote the development of preinvasive mammary lesions. The cancer prevention effect was associated with reduced expression of proliferating cell nuclear antigen, cluster of differentiation 34, and signal transducers and activators of transcription 3 in mammary glands by >80%.

Conclusion: We found that G-CSF was regulated by rhG-CSF both in vitro and in vivo. Identification of G-CSF genes helped us further understand the mechanism by which G-CSF promotes cancer. Low doses of rhG-CSF could significantly increase tumor latency and increase tumor multiplicity and burden. Moreover, rhG-CSF effectively promotes development of both malignant and premalignant mammary lesions in MMTV-erbB2 mice.

No MeSH data available.


Related in: MedlinePlus

rhG-CSF promotes malignant mammary epithelial cell proliferation. (A) Effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the growth of normal and malignant breast cells (MCF-7, SKBR-3 breast cancer cells). We retreated with 0, 0.1, 1, 10, 100, 1,000 µg/L of rhG-CSF. Cell proliferation was measured by Cell Titer 96 Aqueous Cell Proliferation Assay. (B) The expression of granulocyte colony-stimulating factor (G-CSF) was measured by Western blot.
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Figure 1: rhG-CSF promotes malignant mammary epithelial cell proliferation. (A) Effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the growth of normal and malignant breast cells (MCF-7, SKBR-3 breast cancer cells). We retreated with 0, 0.1, 1, 10, 100, 1,000 µg/L of rhG-CSF. Cell proliferation was measured by Cell Titer 96 Aqueous Cell Proliferation Assay. (B) The expression of granulocyte colony-stimulating factor (G-CSF) was measured by Western blot.

Mentions: MCF-10A, MCF-7, and SKBR-3 cells were treated with rhG-CSF (0, 0.01, 0.1, 1, 10, 100, and 1,000 µg/L), and their growth rates were measured (Figure 1A). G-CSFR expression was measured by Western blot (Figure 1B). The results showed that rhG-CSF promoted cell growth, and it had a more profound effect in MCF-7 and SKBR-3 cells than in MCF-10A cells (p=0.002 and p=0.001, respectively). In particular, in MCF-7 cells, when the concentration was 0.1 µg/L, cell proliferation significantly increased, but then decreased with increasing concentration. For SKBR-3 cells, when the concentration was 1 µg/L, the cell proliferation promotion effect was significant. The results showed that rhG-CSF had little effect on normal breast epithelial cells, but it promoted the proliferation of MCF-7 and SKBR-3 cells.


Recombinant Human Granulocyte Colony-Stimulating Factor Promotes Preinvasive and Invasive Estrogen Receptor-Positive Tumor Development in MMTV-erbB2 Mice.

Zhao CL, Zhang GP, Xiao ZZ, Ma ZK, Lei CP, Song SY, Feng YY, Zhao YC, Feng XS - J Breast Cancer (2015)

rhG-CSF promotes malignant mammary epithelial cell proliferation. (A) Effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the growth of normal and malignant breast cells (MCF-7, SKBR-3 breast cancer cells). We retreated with 0, 0.1, 1, 10, 100, 1,000 µg/L of rhG-CSF. Cell proliferation was measured by Cell Titer 96 Aqueous Cell Proliferation Assay. (B) The expression of granulocyte colony-stimulating factor (G-CSF) was measured by Western blot.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4490261&req=5

Figure 1: rhG-CSF promotes malignant mammary epithelial cell proliferation. (A) Effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the growth of normal and malignant breast cells (MCF-7, SKBR-3 breast cancer cells). We retreated with 0, 0.1, 1, 10, 100, 1,000 µg/L of rhG-CSF. Cell proliferation was measured by Cell Titer 96 Aqueous Cell Proliferation Assay. (B) The expression of granulocyte colony-stimulating factor (G-CSF) was measured by Western blot.
Mentions: MCF-10A, MCF-7, and SKBR-3 cells were treated with rhG-CSF (0, 0.01, 0.1, 1, 10, 100, and 1,000 µg/L), and their growth rates were measured (Figure 1A). G-CSFR expression was measured by Western blot (Figure 1B). The results showed that rhG-CSF promoted cell growth, and it had a more profound effect in MCF-7 and SKBR-3 cells than in MCF-10A cells (p=0.002 and p=0.001, respectively). In particular, in MCF-7 cells, when the concentration was 0.1 µg/L, cell proliferation significantly increased, but then decreased with increasing concentration. For SKBR-3 cells, when the concentration was 1 µg/L, the cell proliferation promotion effect was significant. The results showed that rhG-CSF had little effect on normal breast epithelial cells, but it promoted the proliferation of MCF-7 and SKBR-3 cells.

Bottom Line: Cellular and molecular mechanisms of G-CSF action in mammary glands were investigated via immunohistochemistry and reverse transcription polymerase chain reaction.The cancer prevention effect was associated with reduced expression of proliferating cell nuclear antigen, cluster of differentiation 34, and signal transducers and activators of transcription 3 in mammary glands by >80%.We found that G-CSF was regulated by rhG-CSF both in vitro and in vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Cancer Institute, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China.

ABSTRACT

Purpose: We investigated whether recombinant human granulocyte colony-stimulating factor (rhG-CSF) could promote the development of preinvasive and invasive breast cancer in mouse mammary tumor virus (MMTV-erbB2) mice with estrogen receptor-positive tumors.

Methods: MMTV-erbB2 mice were randomly divided into three experimental groups with 20 mice in each group. MMTV-erbB2 mice were treated with daily subcutaneous injections of vehicle or rhG-CSF (low-rhG-CSF group, rhG-CSF 0.125 µg; vehicle-rhG-CSF group, normal saline 0.25 µg; and high-rhG-CSF group, rhG-CSF 0.25 µg) at 3 months of age. Cellular and molecular mechanisms of G-CSF action in mammary glands were investigated via immunohistochemistry and reverse transcription polymerase chain reaction.

Results: Low, but not high, rhG-CSF doses significantly accelerated mammary tumorigenesis in MMTV-erbB2 mice. Short-term treatment with rhG-CSF could significantly promote the development of preinvasive mammary lesions. The cancer prevention effect was associated with reduced expression of proliferating cell nuclear antigen, cluster of differentiation 34, and signal transducers and activators of transcription 3 in mammary glands by >80%.

Conclusion: We found that G-CSF was regulated by rhG-CSF both in vitro and in vivo. Identification of G-CSF genes helped us further understand the mechanism by which G-CSF promotes cancer. Low doses of rhG-CSF could significantly increase tumor latency and increase tumor multiplicity and burden. Moreover, rhG-CSF effectively promotes development of both malignant and premalignant mammary lesions in MMTV-erbB2 mice.

No MeSH data available.


Related in: MedlinePlus