title: Stathmin is involved in the cooperative effect of Zoledronic acid and gefitinib on bone homing breast cancer cells in vitro.
abstract: Zoledronic acid (Zol) is the most potent inhibitor of bone resorption among the bisphosphonates and is commonly used for inhibiting bone metastasis. However, it remains unclear whether Zol provides a survival benefit. Recent findings indicate that epidermal growth factor (EGF) signaling is an important mediator of bone metastasis. Thus, we examined the combined effects of Zol and an EGF receptor-tyrosine kinase inhibitor, gefitinib, on the proliferation and invasion of a bone-seeking clone and the breast cancer cell line MDA-MB-231. Combined treatment with Zol and gefitinib synergistically inhibited both invasion and cell proliferation of the bone-seeking clone, but not those of the MDA-MB-231 cells. Two-dimensional difference gel electrophoresis and mass spectrometry demonstrated that stathmin was down-regulated during these cooperative effects. Stathmin is a signal transduction regulatory factor which plays an important role in cell division and malignant tumor development. Our data suggest that stathmin may be a promising target molecule for blocking bone metastasis of breast cancer.
authors.affiliation: Department of Breast Oncology, Tokyo Medical University, Shinjuku, Tokyo, Japan; Department of Basic Pathology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Oda
authors.affiliation: Department of Basic Pathology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Iwaya
authors.affiliation: Department of Basic Pathology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Kikuchi
authors.affiliation: Department of Basic Pathology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Department of Molecular and Cellular Biochemistry, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yoneda
authors.affiliation: Department of Traumatology and Critical Care Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors.forename: Kahoko
authors.initials: K
authors.lastname: Nishikawa
authors.affiliation: Department of Basic Pathology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsubara
authors.affiliation: Department of Breast Oncology, Tokyo Medical University, Shinjuku, Tokyo, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Kohno
keywords: Bone-seeking clone; Cell proliferation; Invasion; Mass spectrometry; Two-dimensional fluorescence difference gel electrophoresis