Activated ras Genes Occur in Human Actinic Keratoses, Premalignant Precursors to Squamous Cell Carcinomas

Spencer, James M.; Kahn, Scott M.; Jiang, Wei; DeLeo, Vincent A.; Weinstein, I B

doi:10.1001/archderm.1995.01690190048009

Cited by 121 publications

(52 citation statements)

References 25 publications

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“…Although there have been some reports of overexpression or alterations in Ron in human cancers, the role of Ron in human skin malignancies is unknown. The malignant skin tumors in this model closely resemble the human equivalent of squamous cell carcinoma and malignant fibrous histiocytoma (Leder et al, 1990); some of these human skin cancers have the same H-ras mutation as in our model (Pierceall et al, 1991;Spencer et al, 1995;Bohle et al, 1996;Sakamoto et al, 2001). Therefore, it may be worthwhile to extrapolate and investigate the status of Ron in human skin carcinomas.…”

Section: Discussionmentioning

confidence: 52%

Ron tyrosine kinase receptor regulates papilloma growth and malignant conversion in a murine model of skin carcinogenesis

et al. 2004

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Recent studies demonstrate that the receptor tyrosine kinase (TK) Ron is tumorigenic when overexpressed and plays a role in regulating skin homeostasis. We hypothesized that Ron signaling promotes skin carcinogenesis. To test this hypothesis, mice deficient in the TK domain of Ron (TK À/À mice) were crossed with v-Ha-ras (Tg.AC) transgenic mice; the resulting TK À/À Tg.AC þ /À mice, and their controls, were utilized in a model of chemically induced Ras-mediated skin carcinogenesis. The mice were treated with 2.5 lg of 12-O-tetradecanoylphorbol-13-acetate applied weekly to the shaved back of 36 control (TK

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Section: Discussionmentioning

confidence: 52%

Ron tyrosine kinase receptor regulates papilloma growth and malignant conversion in a murine model of skin carcinogenesis

et al. 2004

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“…Mutations of ras gene family members have been observed in human squamous cell carcinomas and in actinic keratoses, and the prevalence of these lesions opposite pyrimidine dimers is believed to be a direct consequence of UV exposure [50][51][52][53]. Thus, mutations in both ras and p53 may contribute to the formation of squamous cell carcinoma in vivo.…”

Section: Discussionmentioning

confidence: 99%

Cooperation of p53 loss of function and v-Ha-ras in transformation of mouse keratinocyte cell lines

Azzoli

Sagar

et al. 1998

Mol. Carcinog.

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We previously demonstrated that after transduction with the v-Ha-ras oncogene and grafting onto nude mouse hosts, primary epidermal keratinocytes with a null mutation in the p53 gene form tumors with increased growth rates and predisposition to malignant conversion relative to p53 wild-type keratinocytes (Weinberg WC, et al., Cancer Res 54:5584-5592, 1994). To further explore the cooperation between p53 loss of function and activation of the ras oncogene, cell lines were established from the normal epidermises of newborn and adult p53-null mice, and parallel subclones were reconstituted with the p53val135 temperature-sensitive mutant. Reconstituted lines C, G, N, and V demonstrated functional p53 transcriptional activator activity at the wild-type-permissive temperature of 32 degrees C, compared with the hygromycin-selected control line X and parental p53-null lines NHK4 and AK1b. Hygromycin-selected subclones, but not the parental lines, made normal skin in vivo; all cell lines made carcinomas after introduction of v-Ha-ras, independent of p53 status. These cell lines were compared in vitro at 32 degrees C to maximize the amount of p53val135 in the wild-type conformation. Expression of v-Ha-ras did not consistently alter p53-mediated transcriptional activity, suggesting tat ras acts downstream or independently of p53. No correlation was observed between p53-mediated transcriptional activity and in vitro growth rates, colony formation after exposure to ultraviolet light, or suppression by normal neighboring keratinocytes. However, keratinocyte cell lines devoid of p53 and expressing v-Ha-ras formed colonies in soft agar; this was blocked at 32 degrees C in all cell lines reconstituted with p53val135. These keratinocyte lines provide a model for exploring the role of p53 and the interaction of p53 and ras in keratinocyte transformation.

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“…17 Expression levels of BRAF and Raf kinase inhibitory protein (RKIP) exhibited a decrease in SCC skin tissue compared to normal skin tissue and actinic keratoses. [18][19][20][21][22][23] Moreover, it has been proposed that BRAF gene mutations contribute to cancer development. The RAS gene has been found to carry mutations in SCC at a frequency of 10-20%.…”

Section: Discussionmentioning

confidence: 99%

Eruptive Squamous Cell Carcinomas Associated with BRAF-Inhibitor Therapy in a Patient with Metastatic Melanoma

Ezra

Hamid

Behroozan

2012

Dermatologic Surgery

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Activated ras Genes Occur in Human Actinic Keratoses, Premalignant Precursors to Squamous Cell Carcinomas

Cited by 121 publications

References 25 publications

Ron tyrosine kinase receptor regulates papilloma growth and malignant conversion in a murine model of skin carcinogenesis

Ron tyrosine kinase receptor regulates papilloma growth and malignant conversion in a murine model of skin carcinogenesis

Cooperation of p53 loss of function and v-Ha-ras in transformation of mouse keratinocyte cell lines

Eruptive Squamous Cell Carcinomas Associated with BRAF-Inhibitor Therapy in a Patient with Metastatic Melanoma

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