Etk/Bmx, a tyrosine kinase with a pleckstrin-homology domain, is an effector of phosphatidylinositol 3′-kinase and is involved in interleukin 6-induced neuroendocrine differentiation of prostate cancer cells

Qiu, Yun; Robinson, Dan R.; Pretlow, T. G.; Kung, Hsing-Jien

doi:10.1073/pnas.95.7.3644

Cited by 226 publications

(261 citation statements)

References 43 publications

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“…The dominantnegative (DN) Etk carries a substitution of K444 with R in the catalytic domain which abolishes the kinase activity and in addition, a second mutation in the PH domain which, by analogy with Btk, increases the a nity toward lipid. In transient transfections, EtkDN has proven highly e ective in reducing the endogenous Etk kinase activity, presumably by sequestering the activating lipid moiety (Qiu et al, 1998). We show here that EtkDN is equally e ective when stably transfected into the LNCaP cell line.…”

Section: Development Of Lncap Cells Overexpressing Wild-type and Mutamentioning

confidence: 69%

“…A number of proteins containing a PH domain are shown to bind phosphatidyl inositol polyphosphates and to be activated by PI3-kinase. These include rac-GEF, unconventional PKCs, Akt/PKB, PDK2 and the Btk family of tyrosine kinases (Franke et al, 1995;Cross et al, 1995;August et al, 1997;Li et al, 1997;Qiu et al, 1998;Ma et al, 1998;Falasca et al, 1998;Van Lint et al, 1998). Much of the attention has recently been focused on Akt as a protector against apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…We recently reported that Etk is an e ector of PI3-kinase and plays an important role in IL6-induced signaling in human prostate cancer cells (Qiu et al, 1998). PI3-kinase has been shown to be important for the survival of a number of di erent cell types .…”

Section: Development Of Lncap Cells Overexpressing Wild-type and Mutamentioning

confidence: 99%

“…It was shown that the metabolic products of PI3-kinase, phosphatidyl inositol phosphates, bind a protein modular structure, called the pleckstrin-homology (PH) domain . Several PH-domain-containing proteins are found to be e ectors for PI3-kinase (Franke et al, 1995;Cross et al, 1995;August et al, 1997;Li et al, 1997;Qiu et al, 1998). Of particular relevance is Akt/PKB, a serine/ threonine kinase with an N-terminal PH domain, which was recently shown to phosphorylate and inactivate Bad, a protein involved in the apoptosis pathway.…”

Section: Introductionmentioning

confidence: 99%

“…Likewise, Itk is highly expressed in T-cells and involved in T-cell development. Interestingly, Etk is not expressed in either B or T cells, but rather in epithelial cells, endothelial cells, and monocytes/macrophages (Qiu et al, 1998;Tamagnone et al, 1994;Kaukonen et al, 1996;Weil et al, 1997). It is tempting to think that Etk plays a similar role in the growth, development and antiapoptosis of epithelial cells.…”

Section: Introductionmentioning

confidence: 99%

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Etk/Bmx, a PH-domain containing tyrosine kinase, protects prostate cancer cells from apoptosis induced by photodynamic therapy or thapsigargin

Xue

Qiu

et al. 1999

Oncogene

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Prostate carcinoma (PCA) is the most frequently diagnosed malignancy in American men. PCA at advanced stages can both proliferate abnormally and resist apoptosis. Among the many known signal transduction pathways, phosphatidylinositide-3'OH kinase (PI3-kinase) has been shown to play an important role in cell survival and resistance to apoptosis. In this study, we investigate the involvement of Etk/Bmx, a newly discovered tyrosine kinase that is a substrate of PI3-kinase, in protection of prostate cancer cells from apoptosis. Parental LNCaP cells and two derivative cell lines, one overexpressing wild type Etk (Etkwt) and the other expressing a dominant negative Etk (EtkDN), were used to study the function of Etk. The cells were treated with photodynamic therapy (PDT), a newly approved cancer treatment which employs a photosensitizer and visible light to produce an oxidative stress in cells, often leading to apoptosis. Our results indicate that PDT induces apoptosis in LNCaP cells, as measured by DNA fragmentation and by cleavage of poly(ADP-ribose) polymerase (PARP), and moreover, the extent of apoptosis was much reduced in Etkwt cells as compared to LNCaP or EtkDN cells. Assay of overall cell viability con®rmed that Etkwt cells were considerably less sensitive to PDT than were the parental LNCaP or EtkDN cells. Similar results were found in response to thapsigargin (TG). A speci®c inhibitor of PI3-kinase, LY294002, abolished Etk activity and markedly increased TG-induced PARP cleavage. The results suggest that Etk/Bmx is an e cient e ector of PI3-kinase and that the newly described PI3-kinase/Etk pathway is involved in the protection of prostate carcinoma cells from apoptosis in response to PDT or TG.

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Section: Development Of Lncap Cells Overexpressing Wild-type and Mutamentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Development Of Lncap Cells Overexpressing Wild-type and Mutamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Etk/Bmx, a PH-domain containing tyrosine kinase, protects prostate cancer cells from apoptosis induced by photodynamic therapy or thapsigargin

Xue

Qiu

et al. 1999

Oncogene

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Androgen-independent growth is induced by neuropeptides in human prostate cancer cell lines

et al. 2000

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BACKGROUND Androgen‐independent growth leads to progressive prostate cancer after androgen‐ablation therapy. This may be caused by altered specificity of the androgen receptor (AR), by ligand‐independent stimulation of the AR, or by paracrine growth modulation by neuropeptides secreted by neuroendocrine (NE) cells. METHODS We established and characterized the androgen‐independent FGC‐DCC from the androgen‐dependent LNCaP fast growing colony (FGC) cell line. The androgen‐independent DU‐145, FGC‐DCC, and PC‐3, and the androgen‐dependent LNCaP and PC‐346C cell lines were used to study growth modulation of gastrin‐releasing peptide (GRP), calcitonin (CT), serotonin (5‐HT), and vasoactive intestinal peptide (VIP) by 3H‐thymidine incorporation. Specificity of the growth‐modulating effects was tested with the anti‐GRP monoclonal antibody 2A11 and induction of cAMP by neuropeptides. RESULTS Androgen‐independent growth stimulation by neuropeptides was shown in DU‐145 and PC‐346C. 2A11 inhibited GRP‐induced 3H‐thymidine incorporation in DU‐145 and PC‐346C and inhibited proliferation of the FGC‐DCC and PC‐3 cell lines. With some exceptions, cAMP induction paralleled growth stimulation. Dideoxyadenosine (DDA) inhibited the GRP‐induced growth effect in DU‐145 and PC‐346C, whereas oxadiazoloquinoxaline‐1‐one (ODQ) had no effect on 3H‐thymidine incorporation. None of the neuropeptides stimulated growth of LNCaP, FGC‐DCC, or PC‐3. CONCLUSIONS GRP‐induced growth of DU‐145 and PC‐346C was specific and cAMP‐mediated. Androgen‐independent growth of FGC‐DCC cells was mainly due to an induction of Bcl‐2 expression and possibly through the activation of an autocrine and NE‐like pathway, as has been shown also for the PC‐3 cell line. Growth induction of non‐NE cells by neuropeptides could be a possible role for NE cells in clinical prostate cancer. Prostate 42:34–44, 2000. © 2000 Wiley‐Liss, Inc.

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STAT3 mediates IL-6-induced neuroendocrine differentiation in prostate cancer cells

2000

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Etk/Bmx, a tyrosine kinase with a pleckstrin-homology domain, is an effector of phosphatidylinositol 3′-kinase and is involved in interleukin 6-induced neuroendocrine differentiation of prostate cancer cells

Cited by 226 publications

References 43 publications

Etk/Bmx, a PH-domain containing tyrosine kinase, protects prostate cancer cells from apoptosis induced by photodynamic therapy or thapsigargin

Etk/Bmx, a PH-domain containing tyrosine kinase, protects prostate cancer cells from apoptosis induced by photodynamic therapy or thapsigargin

Androgen-independent growth is induced by neuropeptides in human prostate cancer cell lines

STAT3 mediates IL-6-induced neuroendocrine differentiation in prostate cancer cells

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