Expression and cellular localization of TSC-22 in normal salivary glands and salivary gland tumors: Implications for tumor cell differentiation

Abstract

TGF-ß-stimulated clone-22 (TSC-22) was reported to be a differentiation-inducing factor which negatively regulates the growth of salivary gland cancer cells. In the present study, we examined the expression of TSC-22 in salivary gland tumors by immunohistochemistry. In pleomorphic adenoma (PA), most of the sparse myoepitheliallike tumor cells, which are considered as the differentiated cells because they produce extracellular matrix, expressed TSC-22. However, only a limited number of cases of the solid myoepithelial-like tumor cells in PA, which are considered as the growing cells, expressed TSC-22. In adenoid cystic carcinoma (ACC), inner ductal cells in the tubular structure, strongly expressed TSC-22, though the outer myoepithelial-like tumor cells did not express TSC-22. In the cribriform structure, myoepithelial-like tumor cells did not express TSC-22. However, a small ductal structure in the micro-cyst wall strongly expressed TSC-22. Sparse type myoepithelial-like tumor cells in ACC also expressed TSC-22. In mucoepidermoid carcinoma, epidermoid tumor cells and mucous-producing tumor cells in mucoepidermoid carcinoma frequently expressed TSC-22. Thus, the expression of TSC-22 was frequently observed in the cells with differentiatedphenotypes, although rarely in the cells with growing potentials. These results suggest that TSC-22 may play an important role in maintaining the differentiated phenotype in salivary gland tumors.

TSC-22 Promotes Transforming Growth Factor β-Mediated Cardiac Myofibroblast Differentiation by Antagonizing Smad7 Activity

“…Consistently, gene targeting of TSC-22 enhanced the proliferation of hematopoietic precursor cells (HPCs) (40). In addition, TSC-22 was also reported to promote cell differentiation and apoptosis (7,18). Moreover, the Drosophila homolog of TSC-22 was suggested to be in the same genetic pathway as Dpp (a bone morphogenetic protein [BMP] homolog) during fly eye development (33), and it was also shown to induce erythroid cell differentiation by facilitating TGF-␤ signaling (4).…”

Identification of Fat4 and Tsc22d1 as Novel Candidate Genes for Spontaneous Pulmonary Adenomas

“…Fat4 — originally described as a tumor suppressor in Drosophila — was later shown to be a candidate tumor suppressor gene in breast cancer cell lines and primary tumors (40). Tsc22d1 is also a known tumor suppressor by promoting cell growth, survival, and proliferation and by preventing apoptosis, and has been associated with several cancers types (e.g., breast cancer, salivary gland cancer, prostate cancer) (41–43). It has been shown to be highly expressed in the lung (44).…”

The transcriptional programme of contact‐inhibition

“…Vice versa, downregulation of TSC-22 enhances cellular proliferation in human salivary gland cancer cell lines in vitro and in vivo Nakashiro et al, 1998]. Accordingly, a decrease in TSC-22 is observed in several tumours such as large granular lymphocyte leukaemia, glioblastomas, salivary gland and prostate carcinomas [Shostak et al, 2003;Rentsch et al, 2006;Doi et al, 2008;Yu et al, 2009] as well as during chemically induced liver carcinogenesis [Iida et al, 2005] and was identified as an acute molecular marker of non-genotoxic rodent hepatocarcinogenesis [Michel et al, 2005;Fielden et al, 2007]. In line with an inhibitory role of TSC-22 in cell proliferation, we detected a threefold induction of TSC-22 protein in confluent NIH3T3 cells.…”