Low Androgen Sensitivity Is Associated With Low Levels of Akt Phosphorylation in LNCaP‐E9 Cells

Iguchi, Kazuhiro; Fukami, Kazuhiro; Ishii, Kenichiro; Otsuka, Takashi; Usui, Shigeyuki; Sugimura, Yoshiki; Hirano, Kazuyuki

doi:10.2164/jandrol.111.013888

Cited by 7 publications

(10 citation statements)

References 16 publications

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“…We found that VEGF secretion from IL‐6‐treated PCa cells was regulated by the PI3K/AKT signaling pathway. We have recently reported that the low level of Akt phosphorylation was associated with the androgen‐low sensitivity of E9 cells . It is usual that responses to IL‐6 treatment may depend on the different content of membrane IL‐6Rs in PCa cells, although our results showed that responses to IL‐6 treatment on VEGF secretion might be dependent on the level of cellular PI3K/AKT signaling.…”

Section: Discussioncontrasting

confidence: 56%

Interleukin‐6 induces VEGF secretion from prostate cancer cells in a manner independent of androgen receptor activation

et al. 2018

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Section: Discussioncontrasting

confidence: 56%

Interleukin‐6 induces VEGF secretion from prostate cancer cells in a manner independent of androgen receptor activation

et al. 2018

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“…To find evidence to support this hypothesis, we first employed 3D SIM imaging to evaluate the level of Golgi disorganization. In addition to PC-3 cells, we used high-passage LNCaP cells (c-123), similar to PC-3 in terms of androgen-unresponsiveness (Iguchi, Fukami et al, 2012, Lin, Hu et al, 2003. In low passage LNCaP (c-28) cells, Golgi is consistent with its classical structure and positioning, and virtually no Golgi fragments were observed.…”

Section: Resultsmentioning

confidence: 99%

Golgi Renaissance: the pivotal role of the largest Golgi protein giantin

Petrosyan

Manca

Casey

et al. 2018

Preprint

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Golgi undergoes disorganization in response to the drugs or alcohol, but it is able to restore compact structure under recovery. This self-organization mechanism remains mostly elusive, as does the role of giantin, the largest Golgi matrix dimeric protein. Here, we found that in cells treated with Brefeldin A (BFA) or ethanol (EtOH), Golgi disassembly is associated with giantin de-dimerization, which was restored to the dimer form after BFA or EtOH washout. Cells lacking giantin are disabled for the restoration of the classical ribbon Golgi, and they demonstrate altered trafficking of proteins to the cell surface. The fusion of the nascent Golgi membranes is mediated by the cross-membrane interaction of Rab6a GTPase and giantin. Giantin is involved in the formation of long intercisternal connections, which in giantin-depleted cells was replaced by the short bridges that formed via oligomerization of GRASP65. This phenomenon occurs in advanced prostate cancer cells, in which a fragmented Golgi phenotype is maintained by the dimerization of GRASP65. Thus, we provide a model of Golgi Renaissance, which is impaired in aggressive prostate cancer.

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“…Moreover, E9 cells have a more aggressive tumorigenic phenotype than parental LNCaP cells in vivo. We have previously investigated the mechanisms underlying the low androgen sensitivity of E9 cells and found that decreased phosphorylation of Akt was associated with low androgen sensitivity of E9 cells [33]. The Akt and p44/42 MAPK pathways are known to be associated with the regulation of androgen responses [34,35].…”

Section: Discussionmentioning

confidence: 99%

Loss of Fibroblast-Dependent Androgen Receptor Activation in Prostate Cancer Cells is Involved in the Mechanism of Acquired Resistance to Castration

Ishii

Matsuoka

Sasaki

et al. 2019

JCM

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Loss of androgen receptor (AR) dependency in prostate cancer (PCa) cells is associated with progression to castration-resistant prostate cancer (CRPC). The tumor stroma is enriched in fibroblasts that secrete AR-activating factors. To investigate the roles of fibroblasts in AR activation under androgen deprivation, we used three sublines of androgen-sensitive LNCaP cells (E9 and F10 cells: low androgen sensitivity; and AIDL cells: androgen insensitivity) and original fibroblasts derived from patients with PCa. We performed in vivo experiments using three sublines of LNCaP cells and original fibroblasts to form homotypic tumors. The volume of tumors derived from E9 cells plus fibroblasts was reduced following androgen deprivation therapy (ADT), whereas that of F10 or AIDL cells plus fibroblasts was increased even after ADT. In tumors derived from E9 cells plus fibroblasts, serum prostate-specific antigen (PSA) decreased rapidly after ADT, but was still detectable. In contrast, serum PSA was increased even in F10 cells inoculated alone. In indirect cocultures with fibroblasts, PSA production was increased in E9 cells. Epidermal growth factor treatment stimulated Akt and p44/42 mitogen-activated protein kinase phosphorylation in E9 cells. Notably, AR splice variant 7 was detected in F10 cells. Overall, we found that fibroblast-secreted AR-activating factors modulated AR signaling in E9 cells after ADT and loss of fibroblast-dependent AR activation in F10 cells may be responsible for CRPC progression.

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Low Androgen Sensitivity Is Associated With Low Levels of Akt Phosphorylation in LNCaP‐E9 Cells

Cited by 7 publications

References 16 publications

Interleukin‐6 induces VEGF secretion from prostate cancer cells in a manner independent of androgen receptor activation

Interleukin‐6 induces VEGF secretion from prostate cancer cells in a manner independent of androgen receptor activation

Golgi Renaissance: the pivotal role of the largest Golgi protein giantin

Loss of Fibroblast-Dependent Androgen Receptor Activation in Prostate Cancer Cells is Involved in the Mechanism of Acquired Resistance to Castration

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