| Co-Investigator(Kenkyū-buntansha) |
YANASE Toshihiko Kyushu University, Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Associate Professor (30239818)
OKABE Taijirou Kyushu University, Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Research Assistant (40264030)
NAKAMURA Masafumi Kyushu University, Department of Cancer Therapy and Research, Graduate School of Medical Science, Associate Professor (30372741)
大江 賢治 九州大学, 大学病院, 助手 (30419527)
|
|---|
| Budget Amount *help |
¥3,730,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥2,300,000 (Direct Cost: ¥2,300,000)
|
|---|
| Research Abstract |
To explore the treatment of advanced prostate cancer that shows androgen-independent growth, possible interactions between androgen receptor and activin or hedgehog signaling were investigated.
Role of activin receptor in the progression of prostate cancer
The prostate cancer cell lines carrying the plasmid, [EF1 promoter-ActRIB-IRES bGEO], were established in androgen independent prostate cancer cells, ALVA41 (ALVA-ActRIB cells). The cell growth rate was not changed by the expression of ActRIB, However, the histological examination of the xenograft on the back of athymic nude mice revealed that schirrous change was found in the tumor derived from ALVA-ActRIB cells. In addition, there was a positive correlation between the expression levels of ActRIB in the tumor and degree of malignancy. Lymph nodes metastases in the abdominal cavity were frequently found in the mice inoculated with the ALVA-ActRIB cells. Taken together, signaling through activin receptor may play an important role in t
… More
he progression of prostate cancer, thus providing the therapeutic target of advanced prostate cancer.
Cross talk between Androgen receptor signaling and Hedgehog signaling
Sonic hedgehog (SHH) signaling, acting in a combinatorial manner with androgen signaling, is essential for prostate patterning and development. More recently, elevated activation of SHH signaling has been shown to play important roles in proliferation, progression and metastasis of prostate cancer. In this report, we demonstrate for the first time, that GLI1, which has been shown to play a central role in SHH signaling in prostate cancer, can act as a co-repressor to substantially block androgen receptor (AR)-mediated transactivation by directly interacting with AR. Our results suggest that the SHH-GLI pathway might be one of determinants governing the transition of prostate cancer from an androgen-dependent to an androgen-independent state by compensating, or even superseding androgen signaling. Therefore, our observations suggest that targeted disruption of the SHH-GLI pathway, especially by blocking GLI1 activity, is as essential as androgen ablation for counteracting progression of localized tumors to advanced and metastatic forms of prostate cancer, which are incurable by current conventional therapies. Less
|
