Hormonal regulation of PKC-δ protein and mRNA levels in the rabbit corpus luteum

Maizels, Evelyn T.; Shanmugam, Malathy; Lamm, Marilyn; Hunzicker-Dunn, Mary

doi:10.1016/0303-7207(96)03885-3

Cited by 17 publications

(6 citation statements)

References 41 publications

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“…Lin & Chen (1998) have shown that distinct PKC isoforms (PKCε and PKCμ) mediate the activation of adenylyl cyclase activity in RAW264.7 macrophages. Recent studies have also demonstrated an up‐regulation of PKCδ expression in the rat and rabbit corpus luteum by oestrogen (Cutler et al ., 1994; Maizels et al ., 1992; 1996), indicating a role for PKC in the biological response to oestrogen. Since we have previously demonstrated a rapid non‐genomic stimulation of PKC activity in cytosolic fractions of rat distal colonic epithelium (Doolan & Harvey, 1996), it is possible that PKC may be the cytosolic target protein or ‘receptor’ responsible for the rapid response to 17β‐oestradiol.…”

Section: Discussionmentioning

confidence: 99%

Rapid non‐genomic activation of cytosolic cyclic AMP‐dependent protein kinase activity and [Ca²⁺]_i by 17β‐oestradiol in female rat distal colon

Doolan

Condliffe

Harvey

2000

British J Pharmacology

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1 In this study, the e ect of 17b-oestradiol on adenosine 3' : 5'-cyclic monophosphate (cyclic AMP)-dependent protein kinase (PKA) activity was investigated. 2 Rapid (within 15 min) activation of basal PKA activity was observed in cytosolic fractions by 17b-oestradiol but not by 17a-oestradiol, progesterone or testosterone. This stimulation was abolished by the speci®c PKA inhibitor PKI but not by the classical oestrogen receptor antagonist tamoxifen. 3 17b-Oestradiol did not stimulate basal PKA activity in membrane fractions or in cytosolic fractions from male rats. 4 The increase in cytosolic PKA activity was indirect as (i) it was inhibited by the adenylyl cyclase inhibitor SQ22536, (ii) it was mimicked by forskolin and (iii) 17b-oestradiol did not cause a stimulation of basal PKA activity in either type I or type II commercially available PKA holoenzymes. 5 Protein kinase Cd (PKCd) was directly activated by 17b-oestradiol. The speci®c PKC inhibitor, bisindolylmaleimide I (GF 109203X), abolished the 17b-oestradiol-induced PKA activation. 6 17b-Oestradiol stimulated an increase in free intracellular calcium ion concentration ([Ca 2+ ] i ) in isolated female but not male rat colonic crypts. This was inhibited by verapamil, nifedipine and zero extracellular [Ca 2+ ] but una ected by tamoxifen. 17a-Oestradiol, testosterone and progesterone failed to increase [Ca 2+ ] i . 7 PKC and PKA inhibitors abolished the 17b-oestradiol-induced increase in [Ca 2+ ] i . 8 These results demonstrate the existence of a novel 17b-oestradiol-speci®c PKA and Ca 2+ signalling pathway, which is both sex steroid-and gender-speci®c, in rat distal colonic epithelium.

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Section: Discussionmentioning

confidence: 99%

Rapid non‐genomic activation of cytosolic cyclic AMP‐dependent protein kinase activity and [Ca²⁺]_i by 17β‐oestradiol in female rat distal colon

Doolan

Condliffe

Harvey

2000

British J Pharmacology

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“…PKCδ increased proliferative and survival capacities in an immortal- ized mammary cell line (23). Estrogen has been reported to stimulate the expression of PKCδ in the corpus luteum (24), but to downregulate the expression of PKCδ in MCF-7 cells (20). A small molecule PKCδ inhibitor or a dominant-negative PKCδ mutant impaired phorbol ester-induced cell arrest in the G1 phase in SKRB-3 breast cancer cells (25).…”

Section: Introductionmentioning

confidence: 98%

Role of PKC-ERK signaling in tamoxifen-induced apoptosis and tamoxifen resistance in human breast cancer cells

Xie

2012

Oncol Rep

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Abstract. This study was designed to investigate the role of protein kinase C (PKC) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling in tamoxifen (TAM)-induced apoptosis and drug resistance in human breast cancer cells. Drug-sensitive, or estrogen receptor (ER)-positive human breast carcinoma cells (MCF-7) and the multi-drug-resistant variant (ER-negative) MCF-7/ADR cells were treated with doses of TAM for various periods of time. Cell viability and apoptosis were assessed using cell counting, DNA fragmentation and flow cytometric analysis. We found that TAM administration caused a significant increase in apoptosis of MCF-7 cells but not MCF-7/ADR cells. Western blot analysis revealed enhanced expression of PKCδ but decreased expression of PKCα in ER-positive MCF-7 cells; while ER-negative MCF-7/ADR cells had decreased levels of PKCδ and increased levels of PKCα. Interestingly, we observed that in MCF-7 cells, TAM stimulated apoptosis by promoting rapid activation of PKCδ, antagonizing downstream signaling of ERK phosphorylation; while in MCF-7/ADR cells, TAM upregulated PKCα, which promoted ERK phosphorylation. These results suggest that PKCδ enhances apoptosis in TAM-treated MCF-7 cells by antagonizing ERK phosphorylation; while the PKCα pathway plays an important role in TAM-induced drug resistance by activating ERK signaling in MCF-7/ADR cells. The combination of TAM with PKCα and ERK inhibitors could promote TAM-induced apoptosis in breast cancer cells. IntroductionBreast cancer is a common malignancy in females and the second cause of death from cancer in women today (1). Treatment for breast cancer includes surgery, chemotherapy, radiotherapy and endocrine therapy. Tamoxifen (TAM), an antagonist of the estrogen receptor (ER), is a selective ER modulator (SERM). TAM is a front-line endocrine therapeutic drug for ER-positive breast cancers. Results from TAM therapy showed a 40-50% reduction in the risk of cancer recurrence and cancer mortality (2). Recently, TAM has been demonstrated to be effective for some ER-negative breast cancers, as well as other types of cancers, including gliomas. These data suggest that TAM may also be implicated in ER-independent antitumor mechanisms (3,4). Of note, some advanced breast cancers that initially respond well to TAM eventually become refractory to treatment (5-9). Thus, the traditional mechanism of TAM action through the ER is challenged, and other noncanonical pathways need to be explored.Protein kinase C (PKC), a family of serine/threonine kinases, is involved in many important cellular functions, including cell proliferation, migration, differentiation, and apoptosis (10-12). Twelve PKC isoforms have been discovered in various cell types, including conventional PKCs (cPKCα, βI/βII and γ), novel PKCs (nPKCδ, ε, η), and atypical PKCs (aPKCζ) (13,14). The expression of PKCα, δ, ε, η, γ, μ, and ζ has been detected in MCF-7 cells (15,16); PKCα is a marker for anti-estrogen resistance and is involved in the growth of TAM-resistant human breast cancer cell...

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“…Reports on PKCd function in estrogen-responsive tissues are contradictory. PKCd was upregulated by estradiol in corpus luteum (Maizels et al, 1996), while it was downregulated in MCF-7 cells in a time-and dose-dependent manner (Shanmugam et al, 1999). PKCd increased mammary tumour cell growth and metastasis by activation of the Ras/Erk1/2 pathway (Keshamouni et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Impact of PKCδ on estrogen receptor localization and activity in breast cancer cells

et al. 2005

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Regulation of estrogen receptor (ER) function in breast cancer cells is a complex process involving different signalling mechanisms. One signal transduction component that appears to influence ER signalling is protein kinase C (PKC). PKCd is a particular isoenzyme of the novel PKC subfamily that plays a role in growth control, differentiation and apoptosis. The aim of the present study was to investigate the impact of PKCd on the regulation of the transcriptional activity of the human ERa. By using 12-O-tetradecanoylphorbol-13-acetate (TPA), Bryostatin1 and Rottlerin, we show that active PKCd is a proproliferative factor in estrogen-dependent breast cancer cells. Furthermore, activation of PKCd by TPA resulted in activation and nuclear translocation of ERa and in an increase of ER-dependent reporter gene expression. Transfection and expression of the regulatory domain RDd of PKCd, which is inhibitory to PKCd, inhibited the TPA-induced ERa activation and translocation. ERa was not phosphorylated by PKCd; however, glycogen synthase kinase-3 (GSK3) was identified as a substrate of PKCd. The expression of RDd resulted in a decrease of TPA-induced GSK3 phosphorylation and translocation into the nucleus. We suggest that GSK3 plays a role in the PKCd-related nuclear translocation of ERa.

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Hormonal regulation of PKC-δ protein and mRNA levels in the rabbit corpus luteum

Cited by 17 publications

References 41 publications

Rapid non‐genomic activation of cytosolic cyclic AMP‐dependent protein kinase activity and [Ca²⁺]_i by 17β‐oestradiol in female rat distal colon

Rapid non‐genomic activation of cytosolic cyclic AMP‐dependent protein kinase activity and [Ca²⁺]_i by 17β‐oestradiol in female rat distal colon

Role of PKC-ERK signaling in tamoxifen-induced apoptosis and tamoxifen resistance in human breast cancer cells

Impact of PKCδ on estrogen receptor localization and activity in breast cancer cells

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Hormonal regulation of PKC-δ protein and mRNA levels in the rabbit corpus luteum

Cited by 17 publications

References 41 publications

Rapid non‐genomic activation of cytosolic cyclic AMP‐dependent protein kinase activity and [Ca2+]i by 17β‐oestradiol in female rat distal colon

Rapid non‐genomic activation of cytosolic cyclic AMP‐dependent protein kinase activity and [Ca2+]i by 17β‐oestradiol in female rat distal colon

Role of PKC-ERK signaling in tamoxifen-induced apoptosis and tamoxifen resistance in human breast cancer cells

Impact of PKCδ on estrogen receptor localization and activity in breast cancer cells

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Rapid non‐genomic activation of cytosolic cyclic AMP‐dependent protein kinase activity and [Ca²⁺]_i by 17β‐oestradiol in female rat distal colon

Rapid non‐genomic activation of cytosolic cyclic AMP‐dependent protein kinase activity and [Ca²⁺]_i by 17β‐oestradiol in female rat distal colon