Abstract
Abstract Mutational activation of the ras proto-oncogenes is frequently found in skin cancers. However, the nature of downstream signaling pathways from Ras involved in skin carcinogenesis remains poorly understood. Recently, we and others identified phospholipase C (PLC) ε as an effector of Ras. Here we have examined the role of PLCε in de novo skin chemical carcinogenesis by using mice whose PLCε is genetically inactivated. PLCε−/− mice exhibit delayed onset and markedly reduced incidence of skin squamous tumors induced by initiation with 7,12-dimethylbenz(a)anthracene followed by promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). Furthermore, the papillomas formed in PLCε−/− mice fail to undergo malignant progression into carcinomas, in contrast to a malignant conversion rate of approximately 20% observed with papillomas in PLCε+/+ mice. In all of the tumors analyzed, the Ha-ras gene is mutationally activated irrespective of the PLCε background. The skin of PLCε−/− mice fails to exhibit basal layer cell proliferation and epidermal hyperplasia in response to TPA treatment. These results indicate a crucial role of PLCε in ras oncogene-induced de novo carcinogenesis and downstream signaling from TPA, introducing PLCε as a candidate molecular target for the development of anticancer drugs.
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Dates
| Type | When |
|---|---|
| Created | 19 years, 11 months ago (Sept. 20, 2005, 6:44 p.m.) |
| Deposited | 3 years, 2 months ago (June 16, 2022, 5:34 p.m.) |
| Indexed | 1 hour, 15 minutes ago (Sept. 7, 2025, 1:52 p.m.) |
| Issued | 20 years, 8 months ago (Dec. 15, 2004) |
| Published | 20 years, 8 months ago (Dec. 15, 2004) |
| Published Online | 20 years, 8 months ago (Dec. 16, 2004) |
| Published Print | 20 years, 8 months ago (Dec. 15, 2004) |
@article{Bai_2004, title={Crucial Role of Phospholipase Cε in Chemical Carcinogen-Induced Skin Tumor Development}, volume={64}, ISSN={1538-7445}, url={http://dx.doi.org/10.1158/0008-5472.can-04-3143}, DOI={10.1158/0008-5472.can-04-3143}, number={24}, journal={Cancer Research}, publisher={American Association for Cancer Research (AACR)}, author={Bai, Yunfeng and Edamatsu, Hironori and Maeda, Sakan and Saito, Hiromitsu and Suzuki, Noboru and Satoh, Takaya and Kataoka, Tohru}, year={2004}, month=dec, pages={8808–8810} }