Transcriptomics,Genomics

Dataset Information

27

Prkar1a haploinsufficiency leads to an overall increase in tumors caused by other genetic defects or chemical induction


ABSTRACT: [original title] Prkar1a haploinsufficiency in mice leads to an overall increase in tumors caused by other genetic defects or chemical induction We investigated the Prkar1a+/- mice when bred within the Rb1+/- or Trp53+/- genetic backgrounds, or treated with a 2-step skin carcinogenesis protocol. Prkar1a+/-Trp53+/- mice developed more bone sarcomas than Trp53+/- mice (p<0.05) and Prkar1a+/-Rb1+/- mice grew more and larger pituitary and thyroid tumors than Rb1+/- mice. All mice with double heterozygosity had significantly reduced life-spans compared with their single-heterozygous counterparts. Finally, Prkar1a+/- mice developed more papillomas than wild-type animals when treated with a 2-step skin carcinogenesis protocol. A whole-genome transcriptome profiling of tumors produced by all three models identified Wnt signaling as the main pathway activated by abnormal cAMP signaling in these tissues, along with (expected) cell cycle gene abnormalities, all confirmed by qRT-PCR array and immunohistochemical analyses. Overall design: Total RNA obtained from skin papillomas from Prkar1a+/- mice were compared to those obtained from WT mice. Total RNA obtained from pituitary and thyroid tumors from Rb1+/- mice were compared to those samples obtained from Prkar1a+/- Rb1+/- mice. Total RNA obtained from sarcomas from Tp53+/- mice were compared to those samples obtained from Prkar1a+/- Tp53+/- mice.

INSTRUMENT(S): Illumina MouseRef-8 v2.0 expression beadchip

SUBMITTER: Madson Q Almeida  

PROVIDER: GSE19576 | GEO | 2009-12-24

SECONDARY ACCESSION(S): PRJNA122465

REPOSITORIES: GEO

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Publications

Mouse Prkar1a haploinsufficiency leads to an increase in tumors in the Trp53+/- or Rb1+/- backgrounds and chemically induced skin papillomas by dysregulation of the cell cycle and Wnt signaling.

Almeida Madson Q MQ   Muchow Michael M   Boikos Sosipatros S   Bauer Andrew J AJ   Griffin Kurt J KJ   Tsang Kit Man KM   Cheadle Chris C   Watkins Tonya T   Wen Feng F   Starost Matthew F MF   Bossis Ioannis I   Nesterova Maria M   Stratakis Constantine A CA  

Human molecular genetics 20100115 8


PRKAR1A inactivation leads to dysregulated cAMP signaling and Carney complex (CNC) in humans, a syndrome associated with skin, endocrine and other tumors. The CNC phenotype is not easily explained by the ubiquitous cAMP signaling defect; furthermore, Prkar1a(+/-) mice did not develop skin and other CNC tumors. To identify whether a Prkar1a defect is truly a generic but weak tumorigenic signal that depends on tissue-specific or other factors, we investigated Prkar1a(+/-) mice when bred within the  ...[more]

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