Alterations of the
            <i>PPP2R1B</i>
            Gene in Human Lung and Colon Cancer

Wang, Steven Siqing; Esplin, Edward D.; Li, Jia Ling; Huang, Lizhen; Gazdar, Adi F.; Minna, John D.; Evans, Glen A.

doi:10.1126/science.282.5387.284

Cited by 341 publications

(323 citation statements)

References 21 publications

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“…The PP2R1B gene that encodes the b isoform of the A subunit of PP2A is located in a region showing high-frequency LOH. 109 Mutations in the gene encoding the A subunit of PP2A have been found in human breast, lung, colon and colorectal carcinomas, and melanomas. 109,110 These mutations display defective or decreased binding to C subunit or B subunit of PP2A and therefore impair the normal functions of PP2A.…”

Section: Genetic Perturbation and Dysregulation Of The Pi3-k-akt Pathwaymentioning

confidence: 99%

“…109 Mutations in the gene encoding the A subunit of PP2A have been found in human breast, lung, colon and colorectal carcinomas, and melanomas. 109,110 These mutations display defective or decreased binding to C subunit or B subunit of PP2A and therefore impair the normal functions of PP2A. 109,111,112 In addition, expression of the PP2A subunit Bg gene was found to be suppressed in human melanoma.…”

Section: Genetic Perturbation and Dysregulation Of The Pi3-k-akt Pathwaymentioning

confidence: 99%

“…109,110 These mutations display defective or decreased binding to C subunit or B subunit of PP2A and therefore impair the normal functions of PP2A. 109,111,112 In addition, expression of the PP2A subunit Bg gene was found to be suppressed in human melanoma. 113 All of these findings support the notion that PP2A may function as a tumor-suppressor gene.…”

Section: Genetic Perturbation and Dysregulation Of The Pi3-k-akt Pathwaymentioning

confidence: 99%

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The emerging role of the PI3-K-Akt pathway in prostate cancer progression

Ittmann

Ayala

et al. 2005

Prostate Cancer Prostatic Dis

110

112

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The PI3-K-Akt pathway plays a central role in the development and progression of prostate cancer and other malignancies. We review original studies and summarize relevant sections of previous reviews concerning the relationships between abnormalities in the PI3-K-Akt pathway and prostate cancer progression. We discuss laboratory and clinical data that indicate gene perturbation and dysregulation of PI3-K-Akt pathway is common in prostate cancer and other malignancies. We further discuss the critical role of the PI3-K-Akt pathway in the oncogenic signaling network and provide examples that establish the PI3-K-Akt pathway as a focal point for the future development of informative biomarkers and effective therapies for prostate cancer.

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Section: Genetic Perturbation and Dysregulation Of The Pi3-k-akt Pathwaymentioning

confidence: 99%

Section: Genetic Perturbation and Dysregulation Of The Pi3-k-akt Pathwaymentioning

confidence: 99%

Section: Genetic Perturbation and Dysregulation Of The Pi3-k-akt Pathwaymentioning

confidence: 99%

See 1 more Smart Citation

The emerging role of the PI3-K-Akt pathway in prostate cancer progression

Ittmann

Ayala

et al. 2005

Prostate Cancer Prostatic Dis

110

112

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“…Furthermore, the PP2A subunit A per se also has been described to be genetically or functionally altered in different types of cancer. Indeed, mutations of PR65/Ab have been reported in primary lung tumours and in colorectal carcinomas, in which a gene deletion generates a truncated A subunit that is unable to interact with the PP2Ac catalytic subunit (Wang et al, 1998).…”

Section: Protein Phosphatase 2a (Pp2a) a Phosphatase With Tumour Supmentioning

confidence: 99%

ReSETting PP2A tumour suppressor activity in blast crisis and imatinib-resistant chronic myelogenous leukaemia

Perrotti

Neviani

2006

Br J Cancer

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The deregulated kinase activity of p210-BCR/ABL oncoproteins, hallmark of chronic myelogenous leukaemia (CML), induces and sustains the leukaemic phenotype, and contributes to disease progression. Imatinib mesylate, a BCR/ABL kinase inhibitor, is effective in most of chronic phase CML patients. However, a significant percentage of CML patients develop resistance to imatinib and/or still progresses to blast crisis, a disease stage that is often refractory to imatinib therapy. Furthermore, there is compelling evidence indicating that the CML leukaemia stem cell is also resistant to imatinib. Thus, there is still a need for new drugs that, if combined with imatinib, will decrease the rate of relapse, fully overcome imatinib resistance and prevent blastic transformation of CML. We recently reported that the activity of the tumour suppressor protein phosphatase 2A (PP2A) is markedly inhibited in blast crisis CML patient cells and that molecular or pharmacologic re-activation of PP2A phosphatase led to growth suppression, enhanced apoptosis, impaired clonogenic potential and decreased in vivo leukaemogenesis of imatinib-sensitive and -resistant (T315I included) CML-BC patient cells and/or BCR/ABL þ myeloid progenitor cell lines. Thus, the combination of PP2A phosphatase-activating and BCR/ABL kinase-inhibiting drugs may represent a powerful therapeutic strategy for blast crisis CML patients.

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“…1,17 Additional evidence for such a role came from the recent discovery that the gene encoding the A␤ subunit of PP2A, located on chromosome 11q23 in a region showing a high frequency of loss of heterozygosity (LOH), was mutated in 15% of primary lung tumors, 6% of lung tumor-derived cell lines and 15% of primary colon tumors. 21 In addition, both the A␣ and A␤ subunit isoforms of PP2A were found to be genetically altered in a variety of primary human cancers, 22 and mutations were described in the A␤ subunit gene in 4 colon cancer cases. 23 Further support for a role of PP2A in tumor suppression comes from the finding that the BЈ subunit of PP2A binds to the tumor suppressor adenomatous polyposis coli protein (APC) and downregulates the abundance of ␤-catenin in the Wnt signaling pathway, resulting in growth inhibition.…”

mentioning

confidence: 99%

Reduced expression of the A? subunit of protein phosphatase 2A in human gliomas in the absence of mutations in the A? and A? subunit genes

et al. 2001

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Protein phosphatase 2A (PP2A) consists of 3 subunits: the catalytic subunit, C, and the regulatory subunits, A and B. The A and C subunits both exist as 2 isoforms (␣ and ␤) and the B subunit as multiple forms subdivided into 3 families, B, B and B؆. It has been reported that the genes encoding the A␣ and A␤ subunits are mutated in various human cancers, suggesting that they may function as tumor suppressors. We investigated whether A␣ and A␤ mutations occur in human gliomas. Using single strand conformational polymorphism analysis and DNA sequencing, 58 brain tumors were investigated, including 23 glioblastomas, 19 oligodendrogliomas and 16 anaplastic oligodendrogliomas. Only silent mutations were detected in the A␣ gene and no mutations in the A␤ gene. However, in 43% of the tumors, the level of A␣ was reduced at least 10-fold. By comparison, the levels of the B␣ and C␣ subunits were mostly normal. Our data indicate that these tumors contain very low levels of core and holoenzyme and high amounts of unregulated catalytic C subunit.

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Alterations of the PPP2R1B Gene in Human Lung and Colon Cancer

Cited by 341 publications

References 21 publications

The emerging role of the PI3-K-Akt pathway in prostate cancer progression

The emerging role of the PI3-K-Akt pathway in prostate cancer progression

ReSETting PP2A tumour suppressor activity in blast crisis and imatinib-resistant chronic myelogenous leukaemia

Reduced expression of the A? subunit of protein phosphatase 2A in human gliomas in the absence of mutations in the A? and A? subunit genes

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