Establishment and characterization of androgen-independent human prostate cancer LNCaP cell model

Igawa, Tsukasa; Lin, Fen‐Fen; Lee, Ming-Shyue; Karan, Dev; Batra, Surinder K.; Lin, Ming‐Fong

doi:10.1002/pros.10054.abs

Cited by 60 publications

(121 citation statements)

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“…Additionally and perhaps more importantly, endogenous c-Jun is required for the proliferation of androgen-independent LNCaP cells. Utilizing LNCaP cells that were cultured to grow independent of androgens and thereby mimic the hormone-refractory stage of prostate cancer (Lin et al, 1998;Igawa et al, 2002), we have been able to block the growth of these cells, in either the absence or presence of androgens, by siRNA-mediated diminishing of endogenous c-Jun expression. As these cells exhibit c-Jun coactivation of AR-dependent transcription and we have evidence that their proliferation is dependent on AR-regulated gene expression (C Cai and L Shemshedini, unpublished results), it is likely that the proliferative role of endogenous c-Jun in androgen-independent LNCaP cells is mediated via its coactivation function on AR, irrespective of whether androgen is present or not.…”

Section: Discussionmentioning

confidence: 99%

“…c-Jun mediates the proliferation of androgen-independent LNCaP cells To determine the importance of c-Jun in androgenindependent LNCaP cells, we studied androgen-independent LNCaP cells that were established through continuous passage in culture (Lin et al, 1998;Igawa et al, 2002). These cells, C81, closely mimic hormonerefractory prostate cancer and thus proliferate in an androgen-unresponsive manner, whereas C33 are the parental androgen-dependent cells (Igawa et al, 2002).…”

Section: C-jun Coactivation Mediates and Transactivation Inhibits Andmentioning

confidence: 99%

“…These cells, C81, closely mimic hormonerefractory prostate cancer and thus proliferate in an androgen-unresponsive manner, whereas C33 are the parental androgen-dependent cells (Igawa et al, 2002). c-Jun enhances androgen-induced proliferation S-Y Chen et al stability (Yeap et al, 1999).…”

Section: C-jun Coactivation Mediates and Transactivation Inhibits Andmentioning

confidence: 99%

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c-Jun enhancement of androgen receptor transactivation is associated with prostate cancer cell proliferation

Cai

et al. 2006

Oncogene

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Section: Discussionmentioning

confidence: 99%

Section: C-jun Coactivation Mediates and Transactivation Inhibits Andmentioning

confidence: 99%

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c-Jun enhancement of androgen receptor transactivation is associated with prostate cancer cell proliferation

Cai

et al. 2006

Oncogene

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“…The culturing of LNCaP, PC-3, DU 145 and CWR22Rv1 cells and the defining of different passages of LNCaP have been described previously Igawa et al, 2002). MDA PCa2b cells were maintained as described previously (Chen et al, 2007).…”

Section: Cell Culture and Transfectionmentioning

confidence: 99%

“…In androgen-independent human PCa cells, ErbB-2 is greatly activated by tyrosyl phosphorylation, at least in part due to the low or null expression of cellular prostatic acid phosphatase (cPAcP), a prostate-unique tyrosine phosphatase that dephosphorylates ErbB-2 . Increased ErbB-2 activity in PCa cells correlated with their androgen-independent proliferation, anchorage-independent growth and tumorigenicity (Igawa et al, 2002;Veeramani et al, 2005;Chen et al, 2007). ErbB-2 may also promote the adhesion of prostate cells (Vafa et al, 1998) while the underlying molecular basis is not understood.…”

Section: Introductionmentioning

confidence: 99%

ErbB-2 via PYK2 upregulates the adhesive ability of androgen receptor-positive human prostate cancer cells

et al. 2007

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Aberrant regulation in the adhesive ability of cancer cells is closely associated with their metastatic activity. In this study, we examine the role of ErbB-2 in regulating the adhesive ability of androgen receptor (AR)-positive human prostate cancer (PCa) cells, the major cell population of PCa. Utilizing different LNCaP and MDA PCa2b cells as model systems, we found that ErbB-2 activity was correlated with PYK2 activity and adhesive ability in those cells. Increased ErbB-2 expression or activity in LNCaP C-33 cells enhanced PYK2 activation and cell adhesion, while the high PYK2 activity and the rapid adhesion of LNCaP C-81 cells were decreased by diminishing ErbB-2 expression or activity. Knockdown studies revealed the predominant role of ErbB-2 in regulating LNCaP C-81 cell adhesion. Coimmunoprecipitation showed that C-81 cells had increased interaction between ErbB-2 and PYK2. Elevated ErbB-2 activity in LNCaP cells correlated with increased ERK/MAPK activity and enhanced adhesive ability, which were abolished by the expression of K457A-PYK2 mutant or the treatment of PD98059, a MEK inhibitor. In summary, our data suggested that ErbB-2, via PYK2-ERK/MAPK, upregulates the adhesive ability of AR-positive human PCa cells.

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Inactivation of ID4 promotes a CRPC phenotype with constitutive AR activation through FKBP52

et al. 2017

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Castration‐resistant prostate cancer (CRPC) is the emergence of prostate cancer cells that have adapted to the androgen‐depleted environment of the prostate. In recent years, targeting multiple chaperones and co‐chaperones (e.g., Hsp27, FKBP52) that promote androgen receptor (AR) signaling and/or novel AR regulatory mechanisms have emerged as promising alternative treatments for CRPC. We have shown that inactivation of inhibitor of differentiation 4 (ID4), a dominant‐negative helix loop helix protein, promotes de novo steroidogenesis and CRPC with a gene expression signature that resembles constitutive AR activity in castrated mice. In this study, we investigated the underlying mechanism through which loss of ID4 potentiates AR signaling. Proteomic analysis between prostate cancer cell line LNCaP (L+ns) and LNCaP lacking ID4 (L(−)ID4) revealed elevated levels of Hsp27 and FKBP52, suggesting a role for these AR‐associated co‐chaperones in promoting constitutively active AR signaling in L(−)ID4 cells. Interestingly, protein interaction studies demonstrated a direct interaction between ID4 and the 52‐kDa FK506‐binding protein (FKBP52) in vitro, but not with AR. An increase in FKBP52‐dependent AR transcriptional activity was observed in L(−)ID4 cells. Moreover, pharmacological inhibition of FKBP52‐AR signaling, by treatment with MJC13, attenuated the tumor growth, weight, and volume in L(−)ID4 xenografts. Together, our results demonstrate that ID4 selectively regulates AR activity through direct interaction with FKBP52, and its loss, promotes CRPC through FKBP52‐mediated AR signaling.

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Establishment and characterization of androgen-independent human prostate cancer LNCaP cell model

Cited by 60 publications

References 0 publications

c-Jun enhancement of androgen receptor transactivation is associated with prostate cancer cell proliferation

c-Jun enhancement of androgen receptor transactivation is associated with prostate cancer cell proliferation

ErbB-2 via PYK2 upregulates the adhesive ability of androgen receptor-positive human prostate cancer cells

Inactivation of ID4 promotes a CRPC phenotype with constitutive AR activation through FKBP52

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