scholarly journals Extracellular protein kinase A as a cancer biomarker: Its expression by tumor cells and reversal by a myristate-lacking Calpha and RIIbeta subunit overexpression

2000 ◽  
Vol 97 (2) ◽  
pp. 835-840 ◽  
Author(s):  
Y. S. Cho ◽  
Y. G. Park ◽  
Y. N. Lee ◽  
M.-K. Kim ◽  
S. Bates ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Tumor Cells ◽  
Cancer Biomarker ◽  
Extracellular Protein ◽  
Kinase A

scholarly journals Autoantibody Cancer Biomarker: Extracellular Protein Kinase A

2006 ◽  
Vol 66 (18) ◽  
pp. 8971-8974 ◽  
Author(s):  
Maria V. Nesterova ◽  
Natalie Johnson ◽  
Christopher Cheadle ◽  
Susan E. Bates ◽  
Sridhar Mani ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Cancer Biomarker ◽  
Extracellular Protein ◽  
Kinase A

scholarly journals Role of Dosage-Sensitive Sex Reversal, Adrenal Hypoplasia Congenita, Critical Region on the X Chromosome, Gene 1 in Protein Kinase A- and Protein Kinase C-Mediated Regulation of the Steroidogenic Acute Regulatory Protein Expression in Mouse Leydig Tumor Cells: Mechanism of Action

Endocrinology ◽  
2008 ◽  
Vol 150 (1) ◽  
pp. 187-199 ◽  
Author(s):  
Pulak R. Manna ◽  
Matthew T. Dyson ◽  
Youngah Jo ◽  
Douglas M. Stocco
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Tumor Cells ◽  
Orphan Nuclear Receptor ◽  
Star Protein ◽  
Kinase C ◽  
Leydig Tumor Cells ◽  
Steroidogenic Acute Regulatory ◽  
Kinase A

Dosage-sensitive sex reversal, adrenal hypoplasia congenita, critical region on the X chromosome, gene 1 (DAX-1) is an orphan nuclear receptor that has been demonstrated to be instrumental to the expression of the steroidogenic acute regulatory (StAR) protein that regulates steroid biosynthesis in steroidogenic cells. However, its mechanism of action remains obscure. The present investigation was aimed at exploring the molecular involvement of DAX-1 in protein kinase A (PKA)- and protein kinase C (PKC)-mediated regulation of StAR expression and its concomitant impact on steroid synthesis using MA-10 mouse Leydig tumor cells. We demonstrate that activation of the PKA and PKC pathways, by a cAMP analog dibutyryl (Bu)2cAMP [(Bu)2cAMP] and phorbol 12-myristate 13-acetate (PMA), respectively, markedly decreased DAX-1 expression, an event that was inversely correlated with StAR protein, StAR mRNA, and progesterone levels. Notably, the suppression of DAX-1 requires de novo transcription and translation, suggesting that the effect of DAX-1 in regulating StAR expression is dynamic. Chromatin immunoprecipitation studies revealed the association of DAX-1 with the proximal but not the distal region of the StAR promoter, and both (Bu)2cAMP and PMA decreased in vivo DAX-1-DNA interactions. EMSA and reporter gene analyses demonstrated the functional integrity of this interaction by showing that DAX-1 binds to a DNA hairpin at position −44/−20 bp of the mouse StAR promoter and that the binding of DAX-1 to this region decreases progesterone synthesis by impairing transcription of the StAR gene. In support of this, targeted silencing of endogenous DAX-1 elevated basal, (Bu)2cAMP-, and PMA-stimulated StAR expression and progesterone synthesis. Transrepression of the StAR gene by DAX-1 was tightly associated with expression of the nuclear receptors Nur77 and steroidogenic factor-1, demonstrating these factors negatively modulate the steroidogenic response. These findings provide insight into the molecular events by which DAX-1 influences the PKA and PKC signaling pathways involved in the regulation of the StAR protein and steroidogenesis in mouse Leydig tumor cells. The characterization of protein kinase A- and protein kinase C-mediated steroidogenic acute regulatory (StAR) expression and steroidogenesis suggests that the orphan nuclear receptor DAX-1 is an important regulator of the steroidogenic response in Leydig cells.

scholarly journals Mutation of Prkar1a Causes Osteoblast Neoplasia Driven by Dysregulation of Protein Kinase A

2008 ◽  
Vol 22 (2) ◽  
pp. 430-440 ◽  
Author(s):  
Emilia Pavel ◽  
Kiran Nadella ◽  
William H. Towns ◽  
Lawrence S. Lawrence S.
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Tumor Cells ◽  
Bone Tumors ◽  
Skin Pigmentation ◽  
Primary Cultures ◽  
Genetic Defect ◽  
Wnt Signaling Pathway ◽  
Endocrine Tumors ◽  
Kinase A

Abstract Carney complex (CNC) is an autosomal dominant neoplasia syndrome caused by inactivating mutations in PRKAR1A, the gene encoding the type 1A regulatory subunit of protein kinase A (PKA). This genetic defect induces skin pigmentation, endocrine tumors, myxomas, and schwannomas. Some patients with the complex also develop myxoid bone tumors termed osteochondromyxomas. To study the link between the PRKAR1A mutations and tumor formation, we generated a mouse model of this condition. Prkar1a+/− mice develop bone tumors with high frequency, although these lesions have not yet been characterized, either from human patients or from mice. Bone tumors from Prkar1a+/− mice were heterogeneous, including elements of myxomatous, cartilaginous, and bony differentiation that effaced the normal bone architecture. Immunohistochemical analysis identified an osteoblastic origin for the abnormal cells associated with islands of bone. To better understand these cells at the biochemical level, we isolated primary cultures of tumoral bone and compared them with cultures of bone from wild-type animals. The tumor cells exhibited the expected decrease in Prkar1a protein and exhibited increased PKA activity. At the phenotypic level, we observed that tumor cells behaved as incompletely differentiated osteoblasts and were able to form tumors in immunocompromised mice. Examination of gene expression revealed down-regulation of markers of bone differentiation and increased expression of locally acting growth factors, including members of the Wnt signaling pathway. Tumor cells exhibited enhanced growth in response to PKA-stimulating agents, suggesting that tumorigenesis in osteoblast precursor cells is driven by effects directly mediated by the dysregulation of PKA.

scholarly journals Geranylgeraniol enhances testosterone production via the cAMP/protein kinase A pathway in testis-derived I-10 tumor cells

2016 ◽  
Vol 80 (4) ◽  
pp. 791-797 ◽  
Author(s):  
Hsin-Jung Ho ◽  
Hitoshi Shirakawa ◽  
Risa Yoshida ◽  
Asagi Ito ◽  
Misato Maeda ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Tumor Cells ◽  
Testosterone Production ◽  
Kinase A

scholarly journals Cysteine Sulfoxides Enhance Steroid Hormone Production via Activation of the Protein Kinase A Pathway in Testis-Derived I-10 Tumor Cells

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4694
Author(s):  
Yuya Nakayama ◽  
Hsin-Jung Ho ◽  
Miki Yamagishi ◽  
Hiroyuki Ikemoto ◽  
Michio Komai ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Tumor Cells ◽  
Steroid Hormone ◽  
Hormone Production ◽  
Onion Extract ◽  
Testosterone Levels ◽  
Age Related ◽  
Cysteine Sulfoxides ◽  
Kinase A

Testosterone plays an important role in male sexual characteristics and maturation, and decreased testosterone levels increase the risk of several diseases. Recently, onion extract rich in cysteine sulfoxides, which are amino acids unique to onions, has been reported to alleviate age-related symptoms resulting from decreased testosterone levels in males. However, the mechanism underlying the suppression of low testosterone levels by cysteine sulfoxides has not been elucidated. In this study, we found that onion extract containing cysteine sulfoxides enhanced progesterone, a precursor of testosterone, in mouse testis-derived I-10 tumor cells. Furthermore, cysteine sulfoxides activated protein kinase A (PKA) and cyclic adenosine monophosphate response element-binding protein, which are key factors in steroidogenesis. These results suggest that cysteine sulfoxides enhance steroid hormone production via activation of the PKA signaling pathway.

scholarly journals The diagnostic value of extracellular protein kinase A (ECPKA) in serum for gastric and colorectal cancer

2020 ◽  
Vol 9 (6) ◽  
pp. 3870-3878
Author(s):  
Yan Wu ◽  
Yafang Li ◽  
Junqiang Liu ◽  
Mengjiao Chen ◽  
Wei Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Diagnostic Value ◽  
Extracellular Protein ◽  
Kinase A

Prediction of Survival in Patients with Non-Hodgkin’s Lymphoma: Role of Tumor Necrosis Factor Ligand-Receptor and Extracellular Protein Kinase A.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4737-4737
Author(s):  
Chul Won Choi ◽  
Soo-Young Yoon ◽  
Hwa Jung Sung ◽  
In Keun Choi ◽  
Seok Jin Kim ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Tumor Necrosis Factor ◽  
Protein Kinase A ◽  
Patient Group ◽  
Tumor Necrosis ◽  
Extracellular Protein ◽  
Control Group ◽  
Necrosis Factor ◽  
Kinase A

Abstract Backgrounds: The International Prognostic Index (IPI) is the most commonly used survival parameter for patients with Non-Hodgkin’s lymphoma (NHL). To investigate an another factor to predict survival, we studied the role of tumor necrosis factor receptor with molecular weight of 75 kd (p75-R-TNF) and extracellular protein kinase A (ECPKA). TNF has a central role in inflammatory processes, and its receptor is constitutively found in the circulation and is elevated in a variety diseases. The cAMP-dependent protein kinase (PKA) is critically involved in the regulation of metabolism, cell growth and differentiation, and gene expression. PKA is a predominantly intracellular enzyme, but it has been shown that cancer cells of various cell types excrete PKA into the conditioned medium. This extracellular form i.e., ECPKA is known to be upregulated in the serum of cancer patients as compared with normal serum. The aim of this prospective study was to evaluate p75-R-TNF and ECPKA as feasible prognostic factors for patients with NHL. Methods: From October 2003 to May 2005, chemotherapy-naive patients with NHL who were planned to receive CEOP-B or R-CHOP chemotherapy at Guro Hospital, Korea University were enrolled. Blood sampling for p75-R-TNF and ECPKA was done before chemotherapy initiation and was stored at −70°C until the assay. The level of p75-R-TNF was measured using ELISA kit. ECPKA was measured by RIA method. A total of 20 serum samples from normal people were used as control. Results: A total of 45 patients were enrolled. The male to female ratio was 22:23, and the median age was 58 years old (range: 29–87). Indolent histologic type and aggressive type were 4 and 41 patients, respectively. Twenty-two patients were limited stage (stage I, II) and 23 patients were advanced stage (stage III, IV). The level (mean±SD) of p75-R-TNF was 1066.6±1174.9 pg/ml for patient group and that of control group was 678.2±312.4 pg/ml. ECPKA activity of patient group was 87.6±21.1 mU/ml as compared with 40.6±21.5 mU/ml in control group. During the median follow-up period of 8.5 months, 12 patients died and 33 patients were alive. As a result of univariate analysis, serum albumin (p=0.005), hemoglobin (p=0.054), the IPI score [0–2 vs 3–5] (p=0.006), occurrence of febrile neutropenia (p=0.01), and level of p75-R-TNF (p=0.003) were significantly associated with survival. By logistic regression testing, p75-R-TNF level was identified as an independent predictive factor for survival (p=0.037). Median survival of patients with elevated p75-R-TNF (cutoff: 678.2 pg/ml) was 10.5 months. For patients with p75-R-TNF < 678.2 pg/ml, median value was not reached yet. Conclusions: This study indicates that in addition to the IPI, high baseline levels of p75-R-TNF can predict the survival of patients with NHL. The levels of ECPKA were elevated in patient group than those of normal controls, but its level could not predict the prognosis.

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