The Hedgehog pathway is a possible therapeutic target for patients with estrogen receptor-negative breast cancer.
Understanding the expression patterns of estrogen receptor-alpha (ERalpha) is essential for determining therapeutic strategies for patients with breast cancer. The prognosis of patients with ERalpha-negative breast cancer is still poor. We have previously shown that Hedgehog (Hh) signaling is constitutively activated in breast cancer and that Hh signaling could be a new therapeutic target. Therefore, in this study, whether or not Hh signaling could be utilized as a therapeutic target for patients with ERalpha-negative breast cancer was examined. For this purpose, three ERalpha-negative breast cancer cell lines were used in which Hh pathway-related molecules such as the ligand Patched1 and the transcriptional factor Gli1 as target cells are expressed. Cyclopamine, an inhibitor of the Hh pathway, significantly suppressed both the cell proliferation and invasion ability of these cancer cells. In addition, the knockdown of Gli1 by RNA interference in these cells also significantly reduced both cell proliferation and invasion ability. Since our previous data have shown a constitutive activation of the Hh pathway in surgically-resected ERalpha-negative breast cancer specimens, the Hh pathway, especially Gli1, may be a useful therapeutic target for patients with ERalpha-negative breast cancer.
Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
Chizu
C
Kameda
Haruo
H
Tanaka
Akio
A
Yamasaki
Masafumi
M
Nakamura
Kenichiro
K
Koga
Norihiro
N
Sato
Makoto
M
Kubo
Syoji
S
Kuroki
Masao
M
Tanaka
Mitsuo
M
Katano
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D049109:Cell Proliferation / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014704:Veratrum Alkaloids / Q000494:pharmacology; D000071676:Zinc Finger Protein GLI1
C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014157:Transcription Factors; D014704:Veratrum Alkaloids; D000071676:Zinc Finger Protein GLI1; C000541:cyclopamine