Open AccessHedgehog signaling pathway mediates the progression of non‐invasive breast cancer to invasive breast cancer
Author(s) -
Souzaki Masae,
Kubo Makoto,
Kai Masaya,
Kameda Chizu,
Tanaka Haruo,
Taguchi Tomoaki,
Tanaka Masao,
Onishi Hideya,
Katano Mitsuo
Publication year - 2011
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2010.01779.x
Subject(s) - gli1 , breast cancer , cancer research , biology , estrogen receptor , cancer , pathology , metastasis , ductal carcinoma , chromosomal translocation , hedgehog signaling pathway , medicine , signal transduction , microbiology and biotechnology , genetics , biochemistry , gene
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. ( Cancer Sci 2011; 102: 373–381)