Alteration ofEgr-1 mRNA during multistage carcinogenesis in mouse skin

Abstract

Immediate early genes, including fos, jun, and early growth response-1 (Egr-1), are induced during cellular response to changes in extracellular environment. These immediate early genes are believed to mediate processes of cell growth and differentiation. In particular, Egr-1 is induced during mitogenic stimulation of a variety of cell types, including fibroblasts, B cells, and epithelial cells. In the present study, we examined Egr-1 gene expression during multistage carcinogenesis in mouse skin. After a single topical treatment with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) to SENCAR mouse skin, Egr-1 mRNA was induced, and maximal induction was observed at 2 h in both epidermis and dermis. Induction of Egr-1 mRNA by TPA was inhibited by fluocinolone acetonide, a potent inhibitor of tumor promotion by TPA. Egr-1 mRNA was present in primary keratinocytes derived from adult SENCAR mice. The keratinocyte cultures were maintained in low Ca(2+) medium, and Egr-1 mRNA levels became significantly elevated after the cultures were switched to high Ca(2+) medium. Additionally, a large proportion of primary papillomas and carcinomas generated from SENCAR mice by standard initiation-promotion regimens exhibited elevated Egr-1 mRNA compared with normal epidermis. Taken together, these data suggest a possible role of Egr-1 during multistage carcinogenesis in mouse skin.

Early growth response-1 is a regulator of DR5-induced apoptosis in colon cancer cells

“…Egr-1 has also been connected to the development of human cancers. It has been proposed to have a role in multistage carcinogenesis in the skin (Riggs et al, 2000). High levels of constitutive Egr-1 expression have been observed in most human prostate cancers and found to correlate with more advanced stages of malignancy and poor prognosis (Eid et al, 1998).…”

Brain-derived neurotrophic factor-, epidermal growth factor-, or A-Raf-induced growth of HaCaT keratinocytes requires extracellular signal-regulated kinase

“…Since the discovery of the Egr-1 gene as an "early growth response gene," research has been directed toward elucidating the function of Egr-1 in growth and proliferation. Induction of Egr-1 gene transcription was monitored in many cell types in response to mitogens (42), and a direct role of Egr-1 during multistage carcinogenesis in the skin has been proposed (33). The fact that genes encoding growth factors, such as insulin-like growth factor II, platelet-derived growth factors A and B, and TGF-␤1, have been identified as target genes of Egr-1 (24,25,40) indicates that Egr-1 may prolong the mitogenic signaling cascade by stimulation of growth factor synthesis.…”

Regulation of life and death by the zinc finger transcription factor Egr‐1

“…Moreover, tumor progression in transgenic mouse models of prostate cancer was reported to be significantly impaired when Egr-1 was lacking (Abdulkadir et al, 2001). Furthermore, a role of Egr-1 during multistage carcinogenesis in the skin has been proposed (Riggs et al, 2000). The fact that genes encoding growth factors such as insulin-like growth factor-II, platelet-derived growth factor A and B, and transforming growth factor-b1 have been identified as target genes of Egr-1 (Khachigian et al, 1995(Khachigian et al, , 1996Svaren et al, 2000) indicates that Egr-1 may continue the mitogenic signaling cascade via stimulation of growth factor synthesis.…”