scholarly journals Minireview: PRKAR1A: Normal and Abnormal Functions

Endocrinology ◽  
2004 ◽  
Vol 145 (12) ◽  
pp. 5452-5458 ◽  
Author(s):  
Ioannis Bossis ◽  
Constantine A. Stratakis
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Skin Pigmentation ◽  
Suppressor Gene ◽  
Carney Complex ◽  
Regulatory Subunit ◽  
Type I ◽  
Dependent Protein ◽  
Main Component ◽  
Degree Of Differentiation

Abstract The type 1α regulatory subunit (RIα) of cAMP-dependent protein kinase (PKA) (coded by the PRKAR1A gene) is the main component of type I PKA, which regulates most of the serine-threonine kinase activity catalyzed by the PKA holoenzyme in response to cAMP. Carney complex (CNC), or the complex of spotty skin pigmentation, myxomas, and endocrine overactivity, is a multiple endocrine (and not only) neoplasia syndrome that is due to PRKAR1A-inactivating mutations. The R1α protein and PRKAR1A mRNA have been found to be up-regulated in a series of cell lines and human and rodent neoplasms, suggesting this molecule’s involvement in tumorigenesis and its potential role in cell cycle regulation, growth, and/or proliferation. Alterations in PKA activity elicit a variety of effects depending on the tissue, developmental stage, degree of differentiation, and cAMP levels. In addition, RIα may have functions independent of PKA. The presence of inactivating germline mutations and the loss of its wild-type allele in some CNC lesions indicate that PRKAR1A might function as a tumor suppressor gene in these tissues, but could PRKAR1A be a classic tumor suppressor gene? Probably not, and this review explains why.

Regulatory subunit type I-? of protein kinase A (PRKAR1A): A tumor-suppressor gene for sporadic thyroid cancer

2002 ◽  
Vol 35 (2) ◽  
pp. 182-192 ◽  
Author(s):  
Fabiano Sandrini ◽  
Ludmila Matyakhina ◽  
Nicholas J. Sarlis ◽  
Lawrence S. Kirschner ◽  
Constantine Farmakidis ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Protein Kinase ◽  
Tumor Suppressor ◽  
Protein Kinase A ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene ◽  
Regulatory Subunit ◽  
Type I ◽  
Kinase A

Protein kinase A and its role in human neoplasia: the Carney complex paradigm.

2004 ◽  
Vol 11 (2) ◽  
pp. 265-280 ◽  
Author(s):  
I Bossis ◽  
A Voutetakis ◽  
T Bei ◽  
F Sandrini ◽  
K J Griffin ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Cushing Syndrome ◽  
Skin Pigmentation ◽  
Suppressor Gene ◽  
Carney Complex ◽  
Regulatory Subunit ◽  
Extensive Literature ◽  
Bilateral Adrenal Hyperplasia ◽  
Kinase A

The type 1 alpha regulatory subunit (R1alpha) of cAMP-dependent protein kinase A (PKA) (PRKAR1A) is an important regulator of the serine-threonine kinase activity catalyzed by the PKA holoenzyme. Carney complex (CNC) describes the association 'of spotty skin pigmentation, myxomas, and endocrine overactivity'; CNC is in essence the latest form of multiple endocrine neoplasia to be described and affects the pituitary, thyroid, adrenal and gonadal glands. Primary pigmented nodular adrenocortical disease (PPNAD), a micronodular form of bilateral adrenal hyperplasia that causes a unique, inherited form of Cushing syndrome, is also the most common endocrine manifestation of CNC. CNC and PPNAD are genetically heterogeneous but one of the responsible genes is PRKAR1A, at least for those families that map to 17q22-24 (the chromosomal region that harbors PRKAR1A). CNC and/or PPNAD are the first human diseases to be caused by mutations in one of the subunits of the PKA holoenzyme. Despite the extensive literature on R1alpha and PKA, little is known about their potential involvement in cell cycle regulation, growth and/or proliferation. The presence of inactivating germline mutations and the loss of its wild-type allele in CNC lesions indicated that PRKAR1A could function as a tumor-suppressor gene in these tissues. However, there are conflicting data in the literature about PRKAR1A's role in human neoplasms, cancer cell lines and animal models. In this report, we review briefly the genetics of CNC and focus on the involvement of PRKAR1A in human tumorigenesis in an effort to reconcile the often diametrically opposite reports on R1alpha.

scholarly journals SAT-LB48 Novel Genetic Variant of Carney Complex With Acromegaly

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Elizabeth Cristiano ◽  
John M Miles ◽  
Rajib Bhattacharya
Keyword(s):  
Genetic Variant ◽  
Skin Pigmentation ◽  
Pituitary Tumors ◽  
Surgical Excision ◽  
Carney Complex ◽  
University Hospital ◽  
Regulatory Subunit ◽  
Endocrine Tumors ◽  
Pituitary Microadenoma ◽  
Dependent Protein

Abstract Objective: To describe an uncommon case of Carney complex with acromegaly secondary to pituitary microadenoma with a novel genetic variant. Background: Carney complex (CNC) is a rare autosomal dominant syndrome characterized by myxomas, pigmented skin and mucosal lesions, as well as multiple endocrine tumors. The etiology is an inactivating mutation of the regulatory subunit type 1A of the cAMP-dependent protein kinase (PRKAR1A). Recently, additional CNC pathologic variants in PRKACA and PRKACB have been identified.[1] Elevated growth hormone (GH) and IGF-1 levels are sometimes seen in patients with CNC, thought to be secondary to somatotroph hyperplasia. However, less than one fifth of patients with CNC have clinical acromegaly. [2] Case: Here we describe a 35-year-old female diagnosed with atrial myxoma after presenting with fatigue in her 20s. After her fatigue failed to resolve following surgical excision, further investigation revealed an ovarian tumor. The patient sought care in Mexico where she underwent radiation for presumed ovarian malignancy. Review of the ovarian lesion biopsy at a university hospital later revealed benign melanocyte proliferation. She subsequently developed amenorrhea and hirsutism which prompted referral to endocrinology. Evaluation revealed coarse facial features, large hands, elevated IGF-1, and positive GH suppression test leading to a diagnosis of acromegaly. Gene sequencing revealed a novel pathologic variant of PRKAR1A consistent with CNC. MRI brain was originally negative for pituitary lesions; however follow up imaging after our visit with the patient showed a hypoenhancing lesion concerning for a pituitary microadenoma. Neurosurgical evaluation is underway. Discussion: Acromegaly with a pituitary adenoma is uncommon in patients with CNC. However, clinicians should have high suspicion for the disease in patients with CNC and other endocrine neoplasia disorders. The diagnosis has many deleterious consequences if not treated early. Additionally, this case represents a novel pathologic variant of PRKAR1A that has not previously been identified in Carney complex. References: 1. Correa, R., P. Salpea, and C.A. Stratakis, Carney complex: an update. Eur J Endocrinol, 2015. 173(4): p. M85-97. 2. Pack, S.D., et al., Genetic and histologic studies of somatomammotropic pituitary tumors in patients with the “complex of spotty skin pigmentation, myxomas, endocrine overactivity and schwannomas” (Carney complex). J Clin Endocrinol Metab, 2000. 85(10): p. 3860-5.

Abstract 5528: The protein phosphatase 2A regulatory subunit PR70 is a gonosomal melanoma tumor suppressor gene

2017 ◽  
Author(s):  
Léon C.L. Van Kempen ◽  
Margaret Redpath ◽  
Mounib Elchebly ◽  
Kathleen Oros Klein ◽  
Andreas Papadakis ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Suppressor Gene ◽  
Regulatory Subunit ◽  
Melanoma Tumor ◽  
Phosphatase 2A

scholarly journals Fusion of the Tumor-Suppressor Gene CHEK2 and the Gene for the Regulatory Subunit B of Protein Phosphatase 2 PPP2R2A in Childhood Teratoma

Neoplasia ◽  
2006 ◽  
Vol 8 (5) ◽  
pp. 413-418 ◽  
Author(s):  
Yuesheng Jin ◽  
Fredrik Mertens ◽  
Carl-Magnus Kullendorff ◽  
loannis Panagopoulos
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Protein Phosphatase ◽  
Suppressor Gene ◽  
Regulatory Subunit ◽  
Protein Phosphatase 2 ◽  
Subunit B

scholarly journals Effect of miR‑215 on the Expression of Tumor Suppressor Gene Rb1 in Retinoblastoma Cell Lines

2020 ◽  
Author(s):  
Liqin SHAO ◽  
Zhangxing SHENG ◽  
Yuefeng ZHU ◽  
Jianchao LI ◽  
Rufa MENG
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Cell Lines ◽  
Suppressor Gene ◽  
Clinicopathological Features ◽  
Retinoblastoma Cell ◽  
Reverse Transcription Quantitative Pcr ◽  
Y79 Cells ◽  
Degree Of Differentiation ◽  
Cancer Tissues

Background: Effect of miR-215 on the expression of tumor suppressor gene retinoblastoma (Rb)1 in Rb cell lines was investigated. Methods: A total of 128 patients were selected. The expression of miR‑215 in cancer and adjacent healthy tissues of the 128 patients was detected by reverse transcription-quantitative PCR (RT-qPCR). HXO‑Rb44 and Y79 cell lines were transfected with miR‑215 analogs or miR‑215 inhibitors, and the expression of Rb1 protein in the cell lines was detected by western blotting. Results: The expression of miR-215 in the adjacent healthy tissues of patients was significantly lower than that in cancer tissues (P<0.001). The expression of miR-215 in Y79 and HXO-Rb44 cells was significantly higher than that in APRE-19 cells (P<0.001). The expression of miR-215 in HXO-Rb44 cells was significantly higher than that in Y79 cells (P<0.001). The expression of miR-215 was statistically different from the degree of differentiation and nerve infiltration (P<0.05). The expression of Rb1 in cancer tissues was significantly lower than that in adjacent tissues (P<0.001), the expression of APRE-19 was significantly higher than that in Y79 and HXO-Rb44 cells (P<0.001), and the expression of Rb1 in HXO-Rb44 cells was significantly higher than that in Y79 cells (P<0.05). There was a negative correlation between miR-215 and Rb1 in the tissues of patients, and Rb1 expression decreased with the increase of miR-215 (r=-0.576, P<0.001). Conclusion: miR‑215 is highly expressed in Rb cell lines, and is related to the clinicopathological features of this disease.

The protein phosphatase 2A regulatory subunit PR70 is a gonosomal melanoma tumor suppressor gene

2016 ◽  
Vol 8 (369) ◽  
pp. 369ra177-369ra177 ◽  
Author(s):  
L. C. L. van Kempen ◽  
M. Redpath ◽  
M. Elchebly ◽  
K. O. Klein ◽  
A. I. Papadakis ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Suppressor Gene ◽  
Regulatory Subunit ◽  
Melanoma Tumor ◽  
Phosphatase 2A

CENP-C: An oncogene or tumor suppressor gene? A possible new tumor marker

2001 ◽  
Vol 120 (5) ◽  
pp. A299-A299
Author(s):  
D KAZANOV ◽  
B STERN ◽  
W PYERIN ◽  
O BOECHER ◽  
H STRUL ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Marker ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene
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