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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

Proliferating cell nuclear antigen (PCNA) expression in mice mammary gland invasive ductal carcinoma (immunohistochemical stain for PCNA, ×200) (A) control group; (B) low-dose group; (C) the high-dose group; (D) positive percentage of proliferation cells.
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Figure 3: Proliferating cell nuclear antigen (PCNA) expression in mice mammary gland invasive ductal carcinoma (immunohistochemical stain for PCNA, ×200) (A) control group; (B) low-dose group; (C) the high-dose group; (D) positive percentage of proliferation cells.

Mentions: Figure 3 shows that low-dose treatments with rhG-CSF did not significantly promote tumor formation. No cutaneous toxicities, weight loss, appetite loss, or skin erythema were observed in mice treated with either rhG-CSF dose.


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)

Proliferating cell nuclear antigen (PCNA) expression in mice mammary gland invasive ductal carcinoma (immunohistochemical stain for PCNA, ×200) (A) control group; (B) low-dose group; (C) the high-dose group; (D) positive percentage of proliferation cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Proliferating cell nuclear antigen (PCNA) expression in mice mammary gland invasive ductal carcinoma (immunohistochemical stain for PCNA, ×200) (A) control group; (B) low-dose group; (C) the high-dose group; (D) positive percentage of proliferation cells.
Mentions: Figure 3 shows that low-dose treatments with rhG-CSF did not significantly promote tumor formation. No cutaneous toxicities, weight loss, appetite loss, or skin erythema were observed in mice treated with either rhG-CSF dose.

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