What does this research mean for the field?

Prkar1a haploinsufficiency acts synergistically with Trp53 or Rb1 loss and chemical carcinogens to accelerate tumorigenesis and reduce lifespan through Wnt signaling activation and cell cycle dysregulation. Novelty: ClaimNovelty.CONFIRMATORY. Consensus alignment: ConsensusAlignment.SUPPORTS_CONSENSUS.

January 15, 2010Human Molecular GeneticsOpen Access

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

Q: What are the key findings of this study?

Prkar1a haploinsufficiency synergized with Trp53+/- or Rb1+/- backgrounds to increase tumor development (e.g., more sarcomas, P<0.05) and significantly reduced life-span.

Q: What is the clinical evidence from this study?

Study design: Other. Population: Tumorigenesis. Intervention: Prkar1a haploinsufficiency vs. Wild-type or single-heterozygous mice (Trp53+/- or Rb1+/-). Primary outcome: Tumor development (sarcomas) (p=<0.05).

View Full Paper

Ask AI

Bookmark

Key result

Prkar1a haploinsufficiency synergizes with Trp53+/- or Rb1+/- backgrounds to increase sarcomas and reduce lifespan.

P<0.05

Population

Prkar1a mice bred within Rb1 or Trp53 backgrounds, wild-type mice, human adrenal cells bearing a…

Comparison

Prkar1a haploinsufficiency combined with Trp53… vs Single-heterozygous counterparts (Trp53 or Rb1…

Design

Preclinical

Authors

MAMadson Q. AlmeidaUniversidade de São Paulo MMMichael MuchowNational Institutes of Health SBSosipatros A. BoikosGeorgetown University

Discussion

Member takes

Implication

Hypothesis-generating in mouse models; leaves open PRKAR1A's role in human sarcoma predisposition pending clinical validation.

Structured PICO

Population

Prkar1a(+/-) mice bred within Rb1(+/-) or Trp53(+/-) backgrounds, wild-type mice, human adrenal cells bearing a PRKAR1A-inactivating mutation, and Prkar1a(+/-) mouse embryonic fibroblasts

Exposure

Prkar1a haploinsufficiency combined with Trp53(+/-) or Rb1(+/-) backgrounds, or chemical carcinogenesis; siRNA down-regulation of Ctnnb1, E2f1 or Cdk4

Comparator

Single-heterozygous counterparts (Trp53(+/-) or Rb1(+/-) mice) and wild-type animals

Outcome

Tumor development (sarcomas, pituitary and thyroid tumors, papillomas) and life-span

Main Result

p-value: p=<0.05

Prkar1a haploinsufficiency acts synergistically with other tumor suppressor gene defects or chemicals to induce tumors via Wnt-signaling activation and cell cycle dysregulation.

Cite This Study

Almeida et al. (2010) studied Tumorigenesis. Prkar1a haploinsufficiency vs. Wild-type or single-heterozygous mice (Trp53+/- or Rb1+/-) was evaluated on Tumor development (sarcomas) (p=<0.05). Prkar1a haploinsufficiency synergized with Trp53+/- or Rb1+/- backgrounds to increase tumor development (e.g., more sarcomas, P<0.05) and significantly reduced life-span.

synapsesocial.com/papers/6aa6ec24246eab12a27f6189 https://doi.org/10.1093/hmg/ddq014

View Full Paper

Ask AI

Bookmark

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

Discussion

Member takes

Implication

Structured PICO

Main Result

Cite This Study

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

Discussion

Member takes

Implication

Structured PICO

Main Result

Cite This Study

Also Consider

Also Consider