We have generated mice with a floxed fak allele under the control of keratin-14-driven Cre fused to a modified estrogen receptor (CreER T2 ). 4-Hydroxy-tamoxifen treatment induced fak deletion in the epidermis, and suppressed chemically induced skin tumor formation. Loss of fak induced once benign tumors had formed inhibited malignant progression. Although fak deletion was associated with reduced migration of keratinocytes in vitro, we found no effect on wound re-epithelialization in vivo. However, increased keratinocyte cell death was observed after fak deletion in vitro and in vivo. Our work provides the first experimental proof implicating FAK in tumorigenesis, and this is associated with enhanced apoptosis.Supplemental material is available at http://www.genesdev.org.

A distinctive variable region 14-positive (V14+) a chain (V.14') of the T-cell antigen receptor is predominantly expressed in multiple mouse subspecies. The VJ14 family has two members, Val4.1 and Val4.2, which differ by only three amino acids at positions 50-52. Based on the EcoRI restriction fragment length polymorphism of the gene encoding V.14, mice can be divided into three groups:type I with an 11.2-kilobase (kb) fragment, type II with a 2.0-kb fragment, and type m with the 2.0-kb and 11.2-kb fragments.Usage of V,14-J.281, where J.281 is an a-chain joining segment, with a one-base, N region dominates at the level of 0.02-1.5% of a chains in all laboratory strains, Mus musculus castaneus, and Mus musculus domesticus but not in Mus musculus molossinus, Mus musculus musculus, and Mus spicilegus samples. The preferential Val4Ja281 expression seems to be due to positive selection because the V-Jjunctional region is always glycine, despite the ability of the V.14 gene to associate with J. other than JL281. As Va14-Ja281 expression is independent of known maijor histocompatibility complex antigens, including H-2, TLA, Qa, and HMIT, the selecting ligand must be a monomorphic molecule of the mouse, expressed in a subspecies-specific manner. Additional observations, such as the expression of homogeneous V.14-J.281 in athymic mice, suggest that the positive selection of V.14' T cells occurs extrathymically.

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The chromosome gene for mouse Mel-18 (mMel-18) protein has been isolated and characterized. The entire mMel-18 gene is composed of thirteen exons spanning about 15 kilobases, in which the protein is encoded by exons 5-13. The "RING-finger" motif of Mel-18 protein that displays a significant evolutionary resemblance to other RING-finger nuclear proteins is encoded by exons 5 and 6. Exon 13 encodes a C-terminal proline/serine-rich domain that is homologous to some transactivator proteins. Sequence analysis of the 5'-flanking region revealed the presence of potential binding sites for transcription factors such as SP-1, NF-1, NF-kappa B and c-myc/max. At least two major cap sites and three minor cap sites were identified by S1 mapping and primer extension analysis. We propose that the mMel-18 gene is regulated by two different types of promoters, the CAAT-TATA box promoter and the GC-rich TATA-less promoter. The 2.4 kb DNA fragment of the 5'-flanking region exhibited constitutive promoter activity when transfected into L cells. By the in situ hybridization method, the mMel-18 gene was assigned to mouse chromosome 10C3.

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