HrasG12V induces follicular thyroid cancer with attenuated MAPK activation and increased latency compared to KrasG12D
Bambach, N. E.; Labella, K.; Jolly, L. A.; Cruz, D. I.; Massol, N.; Di Cristofano, A.; Franco, A. T.
Show abstract
RAS mutations are found in nearly 50% of follicular thyroid cancers (FTCs), frequently accompanied by secondary mutations in the P13K/AKT pathway as tumors advance to more poorly differentiated states. To examine the role that oncogenic Hras plays in thyroid tumor initiation and progression, we developed murine models with thyroid-specific expression of HrasG12V combined with heterozygous or homozygous loss of Pten. Loss of Pten cooperated with HrasG12V in a dose-dependent manner to induce the development of follicular thyroid carcinoma and poorly-differentiated thyroid carcinoma. Histopathology of HrasG12V/PtenHom tumors closely resembled those from the established KrasG12D/PtenHom model, but tumor onset was significantly delayed in HrasG12V/PtenHom mice. At three weeks of age, downregulation of MAPK pathway inhibitors was observed in KrasG12D/PtenHom thyroids, accompanied by increased MAPK pathway activation compared to HrasG12V/PtenHom mice. Furthermore, amplification of oncogenic Ras was found in HrasG12V tumors and cell lines, while allelic balance was maintained in KrasG12D models. These studies demonstrate clear phenotypic differences between mutant Hras and Kras in the thyroid and suggest that delayed MAPK activation may mediate the increased tumor latency observed in the HrasG12V/PtenHom model.
Matching journals
The top 9 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Multiple ETS Factors Participate in the Transcriptional Control of TERT Mutant Promoter in Thyroid Cancers 93%
- Recombinant Human TSH Fails to Induce the Proliferation and Migration of Papillary Thyroid Carcinoma Cell Lines 91%
- Heterogeneity in signaling pathway activity within primary and between primary and metastatic breast cancer 87%
Similar papers in this journal
- Expression based biomarkers and models to classify early and late stage samples of Papillary Thyroid Carcinoma 89%
- Distinct expression patterns of Hedgehog signaling components in mouse gustatory system during postnatal tongue development and adult homeostasis 88%
- Addiction of mesenchymal phenotypes on the FGF/FGFR axis in oral squamous cell carcinoma cells 88%
Similar papers in this journal
- Multiple endocrine defects in adult-onset Sprouty1/2/4 triple knockout mice 89%
- Context-dependent effects of whole-genome duplication during mammary tumor recurrence 89%
- Mast Cell Specific Cyp11a1 Deficiency Promotes T Cell Mediated Immunity and Suppresses Tumour Metastasis in a Mouse Model of Melanoma 88%
Similar papers in this journal
- Thyroid hormone receptor beta inhibits the PI3K-Akt-mTOR signaling axis in anaplastic thyroid cancer via genomic mechanisms 92%
- Spatial Transcriptomic Analysis of Pituitary Corticotroph Tumors Unveils Intratumor Heterogeneity 89%
- Exploring the Link Between Nitrate Exposure and Thyroid Cancer: A Nationwide State-Level Analysis 86%
Similar papers in this journal
- Adversary of DNA integrity: a long non-coding RNA stimulates driver oncogenic chromosomal rearrangement in human thyroid cells 88%
- Distinct oncogenes drive distinct genome and epigenome alterations in human mammary epithelial cells 87%
- Free testosterone and malignant melanoma risk in men: prospective analyses of testosterone and SHBG with 19 cancers in men and postmenopausal women UK Biobank 86%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.