Regulation of PKC δ expression by estrogen and rat placental lactogen-1 in luteinized rat ovarian granulosa cells

Peters, Carl A.; Cutler, Richard E.; Maizels, Evelyn T.; Robertson, May C.; Shiu, Robert P. C.; Fields, Phillip A.; Hunzicker-Dunn, Mary

doi:10.1016/s0303-7207(00)00193-3

Cited by 16 publications

(8 citation statements)

References 57 publications

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“…Androgen-dependent PKCδ up-regulation has been also found in coronary smooth muscle [24]. Interestingly, changes in PKCδ expression have been reported in other models in response to other hormones such as estrogens, vitamins, or mechanical forces [25–28], which like androgens are probably mediated through genomic mechanisms. The ability of androgen to regulate multiple apoptotic proteins [29–31] makes it likely that the impaired apoptotic effect of phorbol esters in androgen-deprived LNCaP cells involves additional mechanisms not necessarily related to PKCδ depletion.…”

Section: Discussionmentioning

confidence: 99%

PKC‐mediated secretion of death factors in LNCaP prostate cancer cells is regulated by androgens

Xiao

Gonzalez-Guerrico

Kazanietz

2008

Molecular Carcinogenesis

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Activation of PKCδ in androgen-dependent LNCaP prostate cancer cells leads to apoptosis via the activation of p38 MAPK and JNK cascades. We have recently shown that treatment of LNCaP cells with phorbol 12-myristate 13-acetate (PMA) leads to a PKCδ-mediated autocrine release of death factors, including the cytokines TNFα and TRAIL, and that conditioned medium (CM) collected from PMA-treated LNCaP cells promotes the activation of the extrinsic apoptotic cascade. Interfering with this autocrine loop either at the level of factor release or death receptor activation/signaling markedly impaired the PMA apoptotic response. In the present study we show that this PKCδ-dependent autocrine mechanism is greatly influenced by androgens. Indeed, upon androgen depletion, which down-regulates PKCδ expression, TNFα and TRAIL mRNA induction and release by PMA are significantly diminished, resulting in a reduced apoptogenic activity of the CM and an impaired ability of the CM to activate p38 MAPK and JNK. These effects can be rescued by addition of the synthetic androgen R1881. Furthermore, RNAi depletion of the androgen-receptor (AR) from LNCaP cells equally impaired PMA responses, suggesting that PKC-mediated induction of death factor secretion and apoptosis in LNCaP prostate cancer cells are highly sensitive to hormonal control.

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Section: Discussionmentioning

confidence: 99%

PKC‐mediated secretion of death factors in LNCaP prostate cancer cells is regulated by androgens

Xiao

Gonzalez-Guerrico

Kazanietz

2008

Molecular Carcinogenesis

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“…Notably, changes in the expression of PKC isozymes, including PKCy, have been reported in various pathologic conditions, including cancer, as well as in response to a number of physiologic and pharmacologic stimuli (21)(22)(23). Although PKCy expression could be modulated by estrogens, vitamin D3, or mechanical forces, presumably through genomic mechanisms (24)(25)(26)(27), there is surprisingly very limited knowledge regarding the functional elements in the human PKCd gene promoter or the nature of the factors that control PKCd gene transcription.…”

Section: Introductionmentioning

confidence: 99%

Androgens Regulate Protein Kinase Cδ Transcription and Modulate Its Apoptotic Function in Prostate Cancer Cells

Gavrielides¹,

Gonzalez-Guerrico²,

Riobó

et al. 2006

Cancer Research

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Activation of protein kinase CD (PKCD), a member of the novel PKC family, leads to apoptosis in several cell types. Although the molecular bases of PKCD activation are being unfolded, limited information is available on the mechanisms that control its expression. Here, we report that in prostate cancer cells PKCD is tightly regulated by androgens at the transcriptional level. Steroid depletion from the culture medium causes a pronounced down-regulation of PKCD protein and mRNA in androgen-sensitive LNCaP prostate cancer cells, an effect that is rescued by the androgen R1881 in an androgen receptor (AR)-dependent manner. Analysis of the PKCd promoter revealed a putative androgen responsive element (ARE) located 4.7 kb upstream from the transcription start site. Luciferase reporter assays show that this element is highly responsive to androgens, and mutations in key nucleotides in the AR-binding consensus abolish reporter activity. Furthermore, using chromatin immunoprecipitation assays, we determined that the AR binds in vivo to the PKCD ARE in response to androgen stimulation. Functional studies revealed that, notably, androgens modulate phorbol 12-myristate 13-acetate (PMA)-induced apoptosis in LNCaP cells, an effect that is dependent on PKCD. Indeed, androgen depletion or AR RNA interference severely impaired the apoptotic function of PKCD or the activation of p38, a downstream effector of PKCD in LNCaP cells-effects that can be rescued by restoring PKCD levels using an adenoviral delivery approach. Our studies identified a novel hormonal mechanism for the control of PKCD expression via transcriptional regulation that fine-tunes the magnitude of PKCD apoptotic responses. (Cancer Res 2006; 66(24): 11792-801)

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“…Evidence suggests that diverse stimuli can induce PKC␦ expression (33)(34)(35)(37)(38)(39), but the detailed mechanisms responsible for transcriptional regulation of PKC␦, especially in neuronal cells, have never been explored. The PKC␦ promoter is surprisingly complex and does not contain a TATA box.…”

mentioning

confidence: 99%

Transcriptional Regulation of Pro-apoptotic Protein Kinase Cδ

Jin

Kanthasamy

Anantharam

et al. 2011

Journal of Biological Chemistry

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We previously demonstrated that protein kinase C␦ (PKC␦; PKC delta) is an oxidative stress-sensitive kinase that plays a causal role in apoptotic cell death in neuronal cells. Although PKC␦ activation has been extensively studied, relatively little is known about the molecular mechanisms controlling PKC␦ expression. To characterize the regulation of PKC␦ expression, we cloned an ϳ2-kbp 5-promoter segment of the mouse Prkcd gene. Deletion analysis indicated that the noncoding exon 1 region contained multiple Sp sites, including four GC boxes and one CACCC box, which directed the highest levels of transcription in neuronal cells. In addition, an upstream regulatory region containing adjacent repressive and anti-repressive elements with opposing regulatory activities was identified within the region ؊712 to ؊560. PKC represents a large family of at least 12 serine/threonine kinases that participate in a wide variety of cellular events, including proliferation, cell cycle progression, differentiation, and apoptosis (1). Based on their structure and substrate requirements, PKC isoforms are divided into the following three groups: conventional PKCs (␣, ␤I, ␤II, and ␥), novel PKCs (␦, ⑀, , and ), and atypical PKCs ( and /). As a novel PKC, PKC␦ has been recognized as a key pro-apoptotic effector in various cell types (2, 3). The role of PKC␦ in nervous system function is beginning to emerge, and recent studies show that PKC␦ plays a role in regulation of receptor and channel activity, differentiation, migration, and apoptosis (4). In addition to lipid-mediated activation and phosphorylation activation, a new pathway of PKC␦ activation, proteolytic cleavage, was discovered recently. Previously, we showed that PKC␦ is an oxidative stress-sensitive kinase and that persistent activation of PKC␦ by caspase-3-mediated proteolytic cleavage is a key mediator in oxidative stress-induced dopaminergic neurodegeneration (5-9). Alternatively, pharmacological inhibition of PKC␦ and depletion of PKC␦ by siRNA are each sufficient to prevent dopaminergic neurodegeneration in cell culture and animal models of Parkinson disease (10 -12). We also showed that PKC␦ negatively regulates tyrosine hydroxylase activity and dopamine synthesis by enhancing protein phosphatase 2A activity in dopaminergic neurons (13). An elevated striatal dopamine level was observed in PKC␦ knock-out mice as compared with wild-type mice, further demonstrating a key role of the kinase in the nigrostriatal dopaminergic function (13). In addition, increased PKC␦ activity, caused by aberrant expression of PKC␦, has been implicated in disease conditions, such as ischemia/hypoxia (14 -17) and cancer (18 -28). Therefore, an understanding of the molecular mechanisms that control the amount and activity of PKC␦ is of physiological and pathophysiological interest.PKC␦ is ubiquitously expressed although the expression pattern is varied and complex (29 -32). Evidence suggests that diverse stimuli can induce PKC␦ expression (33)(34)(35)(37)(38)(39), but the detailed mechanisms...

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Regulation of PKC δ expression by estrogen and rat placental lactogen-1 in luteinized rat ovarian granulosa cells

Cited by 16 publications

References 57 publications

PKC‐mediated secretion of death factors in LNCaP prostate cancer cells is regulated by androgens

PKC‐mediated secretion of death factors in LNCaP prostate cancer cells is regulated by androgens

Androgens Regulate Protein Kinase Cδ Transcription and Modulate Its Apoptotic Function in Prostate Cancer Cells

Transcriptional Regulation of Pro-apoptotic Protein Kinase Cδ

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