Mutually exclusive mutations of the Pten and ras pathways in skin tumor progression
Open Access
- 1 August 2004
- journal article
- research article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 18 (15) , 1800-1805
- https://doi.org/10.1101/gad.1213804
Abstract
Pten heterozygous (Pten+/-) mice develop increased papilloma numbers and show decreased carcinoma latency time in comparison with controls after skin treatment with dimethyl benzanthracene (DMBA) and tetradecanoyl-phorbol acetate (TPA). H-ras mutation is normally a hallmark of DMBA-TPA-induced skin tumors, but 70% of carcinomas from Pten+/- mice do not exhibit this mutation, and in all cases have lost the wild-type Pten allele. Tumors that retain the Pten wild-type allele also have H-ras mutations, indicating that activation of H-ras and complete loss of Pten are mutually exclusive events in skin carcinomas. Mitogen-activated protein kinase (MAPK) is consistently activated in the tumors with H-ras mutations, but is strongly down-regulated in Pten-/- tumors, suggesting that this pathway is dispensable for skin carcinoma formation. These data have important implications in designing individual therapeutic strategies for the treatment of cancer.Keywords
This publication has 32 references indexed in Scilit:
- High Intensity ras Signaling Induces Premature Senescence by Activating p38 Pathway in Primary Human FibroblastsJournal of Biological Chemistry, 2004
- Mutations of the BRAF gene in human cancerNature, 2002
- Cowden Syndrome – Diagnostic Skin SignsDermatology, 2001
- Targeted deletion of the H-ras gene decreases tumor formation in mouse skin carcinogenesisOncogene, 2000
- Lack of somatic mutation in the PTEN gene in squamous cell carcinomas of human skinJournal of Dermatological Science, 1999
- Mutation ofPten/Mmac1in mice causes neoplasia in multiple organ systemsProceedings of the National Academy of Sciences, 1999
- Negative Regulation of PKB/Akt-Dependent Cell Survival by the Tumor Suppressor PTENCell, 1998
- Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancersNature Genetics, 1997
- PTEN , a Putative Protein Tyrosine Phosphatase Gene Mutated in Human Brain, Breast, and Prostate CancerScience, 1997
- Oncogenic ras Provokes Premature Cell Senescence Associated with Accumulation of p53 and p16INK4aCell, 1997