The role of protein kinase C (PKC) in the human aryl hydrocarbon receptor (hAhR) signal transduction pathway was examined in cell lines stably transfected with pGUDLUC6.1, in which luc ϩ is solely controlled by four dioxin-responsive elements (DREs). These cell lines, P5A11 and HG40/6, were derived from HeLa and HepG2 cells respectively. Simultaneous treatment of these cells with 2,3,7,8,-tetrachlorodibenzo-p-dioxin (TCDD) and phorbol-12-myristate-13-acetate (PMA) enhanced transactivation of the reporter construct several-fold relative to cells treated with TCDD alone. PKC inhibitors block the PMA effect and hAhR-mediated signal transduction, demonstrating these processes require PKC activity. Examination of other independently generated, HeLa-derived cell lines stably transfected with pGUDLUC6.1 demonstrates the PMA effect in P5A11 cells is not a clonal artifact. Transient transfections indicate the PMA effect is not due to a luciferase message/gene product stabilization mechanism or stimulation of the basal transcription machinery. Examination of cytosolic preparations demonstrates PKC stimulation or inhibition does not alter hAhR and hAhR nuclear translocator protein levels or TCDD-induced downregulation of hAhR levels. Similarly, examination of nuclear extracts indicated PKC stimulation or inhibition does not alter nuclear AhR levels or hAhR/hAhR nuclear translocator protein heterodimer DRE-binding activity as assessed by electrophoretic mobility shift assay. These results demonstrate a PKCmediated event is required for the hAhR to form a functional transcriptional complex that leads to trans-activation and that the DRE is the minimal DNA element required for PMA to enhance AhR-mediated trans-activation.

Solid and papillary epithelial (SPEN) is an uncommon pancreatic tumor often seen in young females. Although most of these neoplasms have a benign course, SPEN do have malignant potential. Treatment is surgical which is usually feasible either via enucleation or more radical procedures. Below we discuss diagnosis, treatment, and prognosis in detail.

Malignant acrospiroma is an uncommon tumor of the eccrine sweat gland. In contrast to its relatively more common benign counterpart, malignant acrospiroma is highly invasive, often with significant lymphatic and distant metastasis. The establishment of this diagnosis is difficult on both clinical and histopathologic grounds. After diagnosis, wide surgical excision is warranted to completely extirpate these lesions. We report the case of a 66-year-old female with a recurrent malignant acrospiroma. This patient's tumor was removed by wide radical resection, including chest wall excision, followed by reconstructive surgery and radiotherapy. After 16 months there is no evidence of local recurrence or distant metastasis.

The ARNT 1 protein is a member of the bHLH-PAS family of transcription factors and is the central dimerization partner (Fig.