title: Hedgehog signaling pathway mediates the progression of non-invasive breast cancer to invasive breast cancer.
abstract: The purpose of this study is to clarify the contribution of the Hedgehog signaling pathway (Hh pathway) to the progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC). A total of 149 surgically resected mammary disease specimens and 12 sentinel lymph nodes with micro-metastasis (Ly-met) were studied. The degree of Hh pathway activation was estimated from the Gli1 nuclear staining ratio (%Gli1 nuclear translocation) in cancer cells. The invasiveness of breast cancer cells was determined using Matrigel assays. A serial increase of %Gli1 nuclear translocation to IDC from non-neoplastic diseases was confirmed. In tumor specimens, %Gli1 nuclear translocation correlated with the invasiveness of each type of mammary disease and also correlated with invasion-related histopathological parameters. The %Gli1 nuclear translocation in lymph nodes with micro-metastasis was similar to that in primary sites and higher than that in DCIS with microinvasion and DCIS. Blockade of the Hh pathway decreased the invasiveness of breast cancer cells. In IDC, %Gli1 nuclear translocation correlated with the expression of estrogen receptor-α. Estrogen increased %Gli1 nuclear translocation and the invasiveness of estrogen receptor-α-positive cells. The Hh pathway mediates progression from a non-invasive phenotype to an invasive phenotype and %Gli1 nuclear translocation may be useful as a predictive marker for evaluating the ability of invasiveness.
authors.affiliation: Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Masae
authors.initials: M
authors.lastname: Souzaki
authors.forename: Makoto
authors.initials: M
authors.lastname: Kubo
authors.forename: Masaya
authors.initials: M
authors.lastname: Kai
authors.forename: Chizu
authors.initials: C
authors.lastname: Kameda
authors.forename: Haruo
authors.initials: H
authors.lastname: Tanaka
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Taguchi
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
authors.forename: Hideya
authors.initials: H
authors.lastname: Onishi
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Katano
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D042282:Microdissection; D009367:Neoplasm Staging; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D053823:Hedgehog Proteins