Downregulation of putative tumor suppressor gene TSC‐22 in human brain tumors

Abstract

Background and Objectives: Our objective was to identify differentially expressed genes involved in the pathogenesis of glioblastoma multiforme (GBM). Methods: Screening of arrayed human fetal brain and human postnatal brain cDNA libraries was performed by differential hybridization with glioblastoma multiforme and human normal brain cDNAs. Results: Repeated differential hybridization of more than 100 cDNA clones selected by primary screening and analysis of RNA from adult normal brain and glial tumors showed 16 nucleotide sequences differentially expressed between normal brain and brain tumors. Among others, decreased content in astrocytic tumors was determined for TSC-22 mRNA corresponding to cDNA in the ICRFp507J1041 clone from human fetal brain cDNA library. Northern blot hybridization of RNA from different human brain tumors showed very low amounts of TSC-22 mRNA in most investigated samples of GBM, anaplastic astrocytoma, and some other tumors. Complete lack of expression of TSC-22 occurred in one sample of anaplastic astrocytoma, as well as in meningioma, brain sarcoma, sarcomatous meningioma, and oligodendroglioma. The differential expression of TSC-22 gene was confirmed by semiquantitative RT-PCR in 15 samples of astrocytomas WHO grade II-IV and three samples of normal brain. Conclusions: Significantly decreased levels of TSC-22 mRNA in human brain and salivary gland tumors and antiproliferative role of TSC-22 strongly suggest a tumor suppressor role for TSC-22.

TSC22D1 and PSAP predict clinical outcome of tamoxifen treatment in patients with recurrent breast cancer

“…It was originally isolated as a Transforming Growth Factor, beta-1 (TGFb) inducible gene in mouse osteoblasts [13]. TSC22D1 was proposed as a tumor-suppressor gene because it participates in growth inhibition of brain tumors, salivary-gland tumors and prostate cancers [14][15][16]. TSC22D1 was found to be downregulated in the presence of estrogens in MCF7 breast cancer cells [17], which was in concordance with our Spearman rank correlation data.…”

The heterogeneity of meningioma revealed by multiparameter analysis: infiltrative and non-infiltrative clinical phenotypes

“…For several of these pinpointed genes, in the context of diverse specific tumors, downregulation has been correlated with increased invasiveness, tumor progression, or decreased apoptosis. This was already reported for ANXA7 (involved in calcium signaling) (20); CD63 (involved in signal transduction) (21); CEBPD, FOS, HES1, MSX1, TP73 and TSC22D1 (all playing a role at least in transcription) (22)(23)(24)(25)(26)(27); GLG1 (fibroblast growth factor receptor) (28); PLA2G2A (phospholipase activity) (29) and PTPN6 (protein tyrosine phosphatase activity) (30). These data may support the idea that a decreased expression of these genes might be consistent with cellular events that are relevant with the infiltrative behaviors of meningiomas.…”

TSC-22 contributes to hematopoietic precursor cell proliferation and repopulation and is epigenetically silenced in large granular lymphocyte leukemia

“…Previous reports have shown that TSC-22 is down-regulated in salivary gland, brain, and prostate tumors, [15][16][17] but evidence for its down-regulation in leukemia and the mechanism(s) by which it is down-regulated have not been clearly described. Moreover, functional analysis of TSC-22 via the creation of a TSC-22 Ϫ/Ϫ mouse has never been reported.…”

“…6 TSC-22 is able to inhibit cell growth, 9,10 promote apoptosis, [11][12][13] and stimulate the differentiation of leukemia cell lines into monocytes, 14 suggesting that it may act as a putative tumor suppressor gene. TSC-22 has been found to be underexpressed in cancers of the salivary gland, brain, and prostate, [15][16][17] however, the mechanism(s) by which TSC-22 is down-regulated is largely unknown. Further, genetic disruption of the TSC-22 gene with a functional characterization in an animal model has not been reported.…”