Protein kinase A (PK-A) regulatory subunit expression in colorectal cancer and related mucosa

Zhang

et al. 2013

Pathol. Oncol. Res.

The cAMP/PKA signalling events regulated by A-kinase anchoring proteins 10 (AKAP10) is involved in tumorigenesis. Previous study showed that AKAP10 polymorphism (2073 A/G, I646V) was associated with colorectal cancer risk. However, there was no literature reporting the role of AKAP10 in the pathogenesis of colorectal cancer. The aim of the study was to investigate the clinicopathologic significance of A-kinase anchoring proteins 10 (AKAP 10) expression and the relationship with its polymorphism in colorectal cancer. The expression of AKAP10 was determined by immunohistochemical staining (IHC) and western blot assay on colorectal cancer (n=176), adenoma (n=87) and distant normal mucosa (n=72). 176 patients with colorectal cancer were genotyped for AKAP10 2073A/G polymorphism by TaqMan RT-PCR. We found that the positive expression rate of AKAP10 in colorectal cancer (59%) was significantly higher than those in adenoma (39%) and distant normal mucosa (42%) (P=0.004). There was no significant difference between adenoma and distant normal mucosa (P=0.741). Positive AKAP10 staining was correlated with deeper tumor invasion (P<0.001)), lymph nodes metastasis (P=0.022), advanced tumor stage (P<0.001) and poorly differentiated degree (P=0.003). Compared with AA genotype (52%), positive expression of AKAP10 was significantly increased in colorectal cancer patients with the variant (AG+GG) genotypes (68%, P=0.033). It was concluded that AKAP10 may play an important role in the development and progression of colorectal cancer.

Section: Discussionmentioning

confidence: 99%

A-Kinase Anchoring Proteins 10 Expression in Relation to 2073A/G Polymorphism and Tumor Progression in Patients with Colorectal Cancer

Zhang

et al. 2013

Pathol. Oncol. Res.

“…53,54 However, this isoform is constitutively overexpressed in cancer cells and is associated with poor prognosis in human cancers. 55 In contrast, PKA-II is preferentially expressed in normal, well-differentiated tissues. [56][57] This evidence suggests distinct cell functions for each of these 2 PKA isoforms.…”

Section: Discussionmentioning

confidence: 99%

Calcitonin increases invasiveness of prostate cancer cells: Role for cyclic AMP-dependent protein kinase A in calcitonin action

et al. 2005

Calcitonin (CT) is synthesized and secreted in prostate epithelium, and its secretion from malignant prostates is several-fold higher than from benign prostates. CT receptor (CTR) is expressed in malignant prostate epithelium, and its activation stimulates growth of prostate cancer (PC) cells via activation of adenylyl cyclase and calcium/phospholipid pathways. To identify the role of ''CT System'' in prostate cancer, we tested the expression of CT and CTR mRNAs in invading tumor cells of prostate cancer specimens. The effect of CT on in vitro invasion of PC cell lines and on activation of gelatinases was also examined. The cells of primary tumors and those invading stroma co-expressed CT/CTR mRNAs. Exogenously added CT increased in vitro invasion of PC cell lines and caused a rapid, several-fold but transient increase in protein kinase A activity. In contrast, anti-CT serum caused a dose-dependent inhibition of in vitro invasion of PC-3M cells. CT also increased the concentration and activities of MMP-2 and MMP-9. Rp.cAMP, a competitive inhibitor of cAMP-dependent protein kinase A, myristoylated protein kinase A inhibitory peptide (PKI) as well as the expression of dominant negative form of PKA all attenuated basal in vitro invasion of PC-3M cells, and CT could not increase in vitro invasiveness in their presence. These results suggest that overexpression of ''CT System'' in invasive PC tumors significantly contributes to increased invasiveness of prostate cancer cells. The action of CT may be mediated by protein kinase A signaling, which subsequently leads to increased cell invasion and secretion of gelatinases. ' 2005 Wiley-Liss, Inc.Key words: prostate cancer; invasion; calcitonin; PKA; metastasis Calcitonin (CT), a 32 amino acid peptide produced by C cells of mammalian thyroid, has also been detected in human brain, the pituitary gland, lung carcinoma as well as the conditioned media from the cultures of primary prostate epithelial cells.1-6 Although most well-known functions of CT include inhibition of bone resorption, renal regulation of sodium, phosphate, calcium and neuromodulation, 6 CT has also been shown to regulate secretory and proliferative functions of several organs. [7][8][9] Previous studies from this laboratory have shown that immunoreactive CT (iCT) is secreted by primary prostate epithelial cells, and its secretion from cancer-derived primary prostate cells is several-fold higher than that from the cells of benign prostatic hyperplasia origin. 1 We have reported that mRNAs for CT and its receptor (CTR) are selectively localized to the basal epithelium of benign prostates but are distributed throughout the epithelium of malignant prostates. High-affinity CT receptors have been identified in membrane preparations of primary tumors as well as androgen-responsive LNCaP and highly metastatic but androgen refractory PC-3M prostate cancer cells.10 Exogenously added CT stimulates the proliferation of LNCaP cells by stimulating cAMP accumulation and increasing cytoplasmic Ca 21 transients, and CT al...

The Journal of Molecular Diagnostics

“…Expression of R1␣ of PKA is increased in various human cancers including those of breast, 27 ovary, 28 lung, 29 and colon. 30 Furthermore, the pathogenesis of malignancy and poor prognosis in cancer patients has been reported to correlate with overexpression of Rl␣ of the PKA gene. 31 Previous experimental evidence has implicated different roles of regulatory subunits of PKA in the regulation of leukemic cell proliferation and differentiation.…”

Section: Activation Of Multi-signaling Pathways By Atramentioning

confidence: 99%

Gene Expression Profiling during All-trans Retinoic Acid-Induced Cell Differentiation of Acute Promyelocytic Leukemia Cells

Yang

Zhao

et al. 2003

Using cDNA microarrays we determined the gene expression patterns in the human acute promyelocytic leukemia (APL) cell line NB4 during all-trans retinoic acid (ATRA)-induced differentiation. We analyzed the expression of 12,288 genes in the NB4 cells after 12 hours, 24 hours, 48 hours, 72 hours, and 96 hours of ATRA exposure. During this time course, we found 168 up-regulated and more than 179 down-regulated genes, most of which have not been reported before. Many of the altered genes encode products that participate in signaling pathways, cell differentiation, programmed cell death, transcription regulation, and production of cytokines and chemokines. Of interest, the CD52 and protein kinase A regulatory subunit ␣ (PKA-Rl␣) genes, whose products are being used as therapeutic targets for certain human neoplasias in currently ongoing clinical trials, were among the genes observed to be markedly up-regulated after ATRA treatment. The present study provides valuable data to further understand the mechanism of ATRAinduced APL cell differentiation and suggests potential therapeutic alternatives for this leukemia. Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia characterized by the accumulation of cells arrested at the promyelocytic stage of myeloid differentiation. This leukemia exhibits a specific chromosomal translocation t(15;17) involving the promyelocytic leukemia (PML) gene locus on chromosome 15, and the retinoid acid receptor ␣ (RAR␣) locus on chromosome 17. This translocation generates a chimeric fusion gene PML-RAR␣, which encodes a protein that functions as an aberrant nuclear receptor considered to be the cause of APL.