Differential expression of multiple anti‐apoptotic proteins in epidermis of IGF‐1 transgenic mice as revealed by 2‐dimensional gel electrophoresis/mass spectrometry analysis

Abstract

Overexpression of insulin-like growth factor-1 (IGF-1) has been associated with a number of human tumors, including breast, colon, lung, and prostate cancers. In previous studies, we found that mice overexpressing human IGF-1 in the basal layer of the epidermis (BK5.IGF-1 mice) developed skin tumors following treatment with the skin tumor initiator, 7,12-dimethylbenz[a]anthracene, indicating that IGF-1 can act as a skin tumor promoter. In the present study, we employed a proteomics approach of two-dimensional (2-D) gel electrophoresis and mass spectrometry to profile differentially expressed proteins in skin epidermis between BK5.IGF-1 transgenic and nontransgenic littermates. Two-D gels from each of three transgenic and three age/sex matched wild-type littermates were compared at two different pH ranges. Differentially expressed protein spots were identified by Bio-Rad's PDQuest image analysis, in-gel digested, and analyzed on a MALDI-TOF MS system. A total of 23 proteins were identified as differentially expressed, 17 of them overexpressed in transgenic mice. These proteins included 14-3-3 sigma, galectin-7, an apoptosis-related protein, three heat shock proteins, four calcium binding proteins, three proteases or protease inhibitors, one actin regulatory capping protein, and translation initiation factor 5A. The differential expression of GRP78, alpha enolase, and galectin-7 was verified by 1-D western blot analysis. Two-D western blot analyses of alpha enolase and galectin-7 further revealed that alpha enolase had more than one protein spot dependent on charge. The current data suggest that some of the differentially expressed proteins may play a role in the tumor promoting action of IGF-1 in mouse skin.

Molecular carcinogenesis in equine penile cancer: A potential animal model for human penile cancer

“…Recently stromal expression of 14-3-3σ has been demonstrated in endometrial carcinomas and, similar to our results, the neoexpression by fibroblasts in areas of desmoplasia at the IF could be indicative of an active proinvasive environment within the extracellular matrix [40]. To provide more evidence of the role of 14-3-3σ in cancer development, recently it has been shown that 14-3-3σ provides chemoresistance properties to SCC and this fact, along with the anti-apoptotic properties of 14-3-3σ in tumoral cells, highlights the potential of this protein as a very promising biomarker and therapeutic target for penile SCC [18,[41][42][43].…”

The Reciprocal Regulation of γ-Synuclein and IGF-I Receptor Expression Creates a Circuit That Modulates IGF-I Signaling

“…Silencing of SNCG inhibits IGF-I-induced expression of GRP78, an IGF-Iresponsive molecular chaperone (46). Given that GRP78 is a multifunctional protein involved in diverse cellular processes, including the folding and processing of newly synthesized proteins, regulation of calcium homeostasis, modulation of the unfolded protein response, and drug resistance (47), SNCG may indirectly regulate these cellular processes through IGF-IR and GRP78.…”

Induction of matrix metalloproteinase-9 by galectin-7 through p38 MAPK signaling in HeLa human cervical epithelial adenocarcinoma cells

“…IGF-1 transgenic mice developed skin tumors by DMBA, and both the mitogenic and anti-apoptotic pathways were upregulated (21). In the epidermis of IGF-1 transgenic mice, galectin-7 expression was reported to be 3-fold higher, compared to non-transgenic mice (22). Moreover, recently it was reported that galectin-7 is the most up-regulated molecule when benign lymphoma cells progress to the metastatic variant (17).…”