title: Recombinant Human Granulocyte Colony-Stimulating Factor Promotes Preinvasive and Invasive Estrogen Receptor-Positive Tumor Development in MMTV-erbB2 Mice.
abstract: OBJECTIVE
  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%.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Oncology, Cancer Institute, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China.
authors.forename: Chun Ling
authors.initials: CL
authors.lastname: Zhao
authors.affiliation: Department of Oncology, Cancer Institute, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China.
authors.forename: Guang Ping
authors.initials: GP
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Cancer Institute, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China.
authors.forename: Zheng Zheng
authors.initials: ZZ
authors.lastname: Xiao
authors.affiliation: Department of Oncology, Cancer Institute, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China.
authors.forename: Zhi Kun
authors.initials: ZK
authors.lastname: Ma
authors.affiliation: Department of Oncology, Cancer Institute, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China.
authors.forename: Cai Peng
authors.initials: CP
authors.lastname: Lei
authors.affiliation: Department of Oncology, Cancer Institute, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China.
authors.forename: Shi Yuan
authors.initials: SY
authors.lastname: Song
authors.affiliation: Department of Oncology, Cancer Institute, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China.
authors.forename: Ying Ying
authors.initials: YY
authors.lastname: Feng
authors.affiliation: Department of Oncology, Cancer Institute, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China.
authors.forename: Ya Chao
authors.initials: YC
authors.lastname: Zhao
authors.affiliation: Department of Oncology, Cancer Institute, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China.
authors.forename: Xiao Shan
authors.initials: XS
authors.lastname: Feng
keywords: Carcinogenesis; Cell proliferation; Granulocyte colony-stimulating factor; Mammary gland