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Comparative Study
. 2004 Aug 1;18(15):1800-5.
doi: 10.1101/gad.1213804.

Mutually exclusive mutations of the Pten and ras pathways in skin tumor progression

Jian-Hua Mao  1 , Minh D To, Jesus Perez-Losada, Di Wu, Reyno Del Rosario, Allan Balmain
Affiliations
Comparative Study

"VSports手机版" Mutually exclusive mutations of the Pten and ras pathways in skin tumor progression

V体育ios版 - Jian-Hua Mao et al. Genes Dev. .

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) VSports手机版. 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. .

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"V体育官网入口" Figures

Figure 1.
Figure 1.
Pten heterozygosity increases skin cancer susceptibility. (A) Pten protein expression in the skin of wild-type and Pten+/- mice. (B) Expression of Pten is induced in wild-type mice at RNA (top) and protein (bottom) levels at indicated time points after TPA treatment. Pten protein levels in skin of two different mice are shown at each time point. (C) Average papilloma number per mouse at the indicated time points after DMBA-TPA treatment. (D) Latency of carcinoma onset.
Figure 2.
Figure 2.
H-ras and Pten alterations are mutually exclusive. (A) LOH analysis of tumors from Pten+/- mice using the indicated microsatellite markers on chromosome 19, as obtained from the Celera database. Papilloma #16 (fifth from the right) shows loss of distal markers on chromosome 19, but is wild type at Pten, and has a mutation in H-ras (Table 1). (B) Papillomas and carcinomas from wild type (top panel) and Pten+/- (bottom panel) were analyzed for H-ras mutation by digestion of PCR products as described in text, and for Pten expression by RT–PCR. Asterisk indicates samples with TTA alteration, as opposed to the more common CTA, at codon 61 of H-ras, and hence was not digested by XbaI. (C) Chromatogram showing the CAA → TTA alteration at codon 61 of H-ras that occurred in a small number of papillomas.
Figure 3.
Figure 3.
H-ras activation and Pten inactivation elicit differential biochemical responses. The status of pten for each tumor, as determined by microsatellite and RT–PCR analysis, is indicated. (A) Pten and H-Ras protein levels in papillomas and carcinomas. (B) Separation of wild-type and mutant (Gln61Leu) H-Ras protein in carcinomas by high-percentage SDS-PAGE. (C) Analysis of Erk and Akt activation in papillomas and carcinomas using antibodies to detect phosphorylated and total protein, as indicated.
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V体育ios版 - References

    1. Akhurst R.J., Fee, F., and Balmain, A. 1988. Localized production of TGF-β mRNA in tumour promoter-stimulated mouse epidermis. Nature 331: 363-365. - PubMed
    1. Balmain A., Ramsden, M., Bowden, G.T., and Smith, J. 1984. Activation of the mouse cellular Harvey-ras gene in chemically induced benign skin papillomas. Nature 307: 658-660. - PubMed
    1. Camisa C., Bikowski, J.B., and McDonald, S.G. 1984. Cowden's disease. Association with squamous cell carcinoma of the tongue and perianal basal cell carcinoma. Arch. Dermatol. 120: 677-678. - PubMed
    1. Chang F., Steelman, L.S., Shelton, J.G., Lee, J.T., Navolanic, P.M., Blalock, W.L., Franklin, R., and McCubrey, J.A. 2003. Regulation of cell cycle progression and apoptosis by the Ras/Raf/MEK/ERK pathway Int. J. Oncol. 22: 469-480. - PubMed (V体育安卓版)
    1. Cox A.D. and Der, C.J. 2003. The dark side of Ras: Regulation of apoptosis. Oncogene 22: 8999-9006. - PubMed

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