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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

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) promote the proliferation of mammary epithelial cells in vivo. Immunohistochemical (IHC) staining of proliferating cell nuclear antigen (PCNA), CD34 and STAT3 in consecutive slides of mammary glands from vehicle- and rhG-CSF-treated mice (IHC stain for PCNA, ×200).
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Figure 4: Recombinant human granulocyte colony-stimulating factor (rhG-CSF) promote the proliferation of mammary epithelial cells in vivo. Immunohistochemical (IHC) staining of proliferating cell nuclear antigen (PCNA), CD34 and STAT3 in consecutive slides of mammary glands from vehicle- and rhG-CSF-treated mice (IHC stain for PCNA, ×200).

Mentions: To determine the mechanism of rhG-CSF-induced growth, we examined the effect of rhG-CSF on proliferation by measuring PCNA and STAT3 expression in mammary glands obtained after 4 months of treatment. rhG-CSF significantly promoted epithelial cell proliferation by 80% (p=0.001), as determined by PCNA IHC staining (Figure 4). Figure 4 shows the IHC results of PCNA, STAT3, and CD34 from consecutive sections. The percentage of PCNA-positive cells showed substantial variation in the vehicle group ranging from 80% to 5%; however, the median amount was 36.8%. In some samples, the high PCNA levels may be the result of hyperplasia development in erbB2-expressing mammary cells. No statistical difference was observed in STAT3 levels between vehicle and rhG-CSF treatments (data not shown), which indicates that rhG-CSF promoted mammary tumorigenesis, primarily by promoting proliferation. The positive Spearman correlation coefficients were statistically significant in both vehicle and rhG-CSF groups.


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)

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) promote the proliferation of mammary epithelial cells in vivo. Immunohistochemical (IHC) staining of proliferating cell nuclear antigen (PCNA), CD34 and STAT3 in consecutive slides of mammary glands from vehicle- and rhG-CSF-treated mice (IHC stain for PCNA, ×200).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Recombinant human granulocyte colony-stimulating factor (rhG-CSF) promote the proliferation of mammary epithelial cells in vivo. Immunohistochemical (IHC) staining of proliferating cell nuclear antigen (PCNA), CD34 and STAT3 in consecutive slides of mammary glands from vehicle- and rhG-CSF-treated mice (IHC stain for PCNA, ×200).
Mentions: To determine the mechanism of rhG-CSF-induced growth, we examined the effect of rhG-CSF on proliferation by measuring PCNA and STAT3 expression in mammary glands obtained after 4 months of treatment. rhG-CSF significantly promoted epithelial cell proliferation by 80% (p=0.001), as determined by PCNA IHC staining (Figure 4). Figure 4 shows the IHC results of PCNA, STAT3, and CD34 from consecutive sections. The percentage of PCNA-positive cells showed substantial variation in the vehicle group ranging from 80% to 5%; however, the median amount was 36.8%. In some samples, the high PCNA levels may be the result of hyperplasia development in erbB2-expressing mammary cells. No statistical difference was observed in STAT3 levels between vehicle and rhG-CSF treatments (data not shown), which indicates that rhG-CSF promoted mammary tumorigenesis, primarily by promoting proliferation. The positive Spearman correlation coefficients were statistically significant in both vehicle and rhG-CSF groups.

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