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- Title
Impact of IFNα2b upon pSTAT3 and the MEK/ERK MAPK Pathway in Melanoma.
- Authors
Wang, Wenjun; Edington, Howard D.; Jukic, Drazen M.; Rao, Uma N. M.; Land, Stephanie R.; Kirkwood, John M.
- Abstract
High-dose IFNα2b (HDI) was established as the first effective adjuvant therapy for patients with high-risk resected melanoma more than a decade ago, but its fundamental molecular mechanism of action remains unclear. STAT3 and the mitogen activated protein kinases (MAPKs), especially ERK (extracellular signal-regulating kinase) and MEK (MAPK/ERK kinase), play roles in melanoma progression and host immunity. We have therefore evaluated STAT3 and MEK/ERK MAP kinases in patients with regional lymph node metastasis (stage IIIB) of melanoma in the context of a prospective neoadjuvant trial of HDI (UPCI 00-008). In the context of this trial, HDI was administered daily for 20 doses following diagnostic biopsy, and prior to definitive surgery. Immunohistochemistry for pSTAT3, phospho-MEK1/2, phospho-ERK1/2, and EGFR was performed on paired fixed (nine patients) biopsies. HDI was found to down-regulate pSTAT3 ( P = 0.008) and phospho-MEK1/2 ( P = 0.008) levels significantly in tumor cells. Phospho-ERK1/2 was down-regulated by HDI in tumor cells ( P = 0.015), but not in lymphoid cells. HDI down-regulated EGFR ( P = 0.013), but pSTAT3 activation appeared not to be associated with EGFR expression and the MEK/ERK MAPK pathway. We conclude that HDI regulates MAPK signaling differentially in melanoma tumor cells and host lymphoid cells in vivo. STAT3 activation is independent of the EGFR/MEK/ERK signaling pathway.
- Subjects
MELANOMA; ADJUVANT treatment of cancer; MITOGEN-activated protein kinases; CANCER cells; PROTEIN kinases; IMMUNOHISTOCHEMISTRY
- Publication
Cancer Immunology, Immunotherapy, 2008, Vol 57, Issue 9, p1315
- ISSN
0340-7004
- Publication type
Article
- DOI
10.1007/s00262-008-0466-9