[Frontiers in Bioscience 2, a18-25, July 15, 1997]|
DISTINCT TUMOR SPECIFIC EXPRESSION OF TGFB4 (ebaf)*, A NOVEL HUMAN GENE OF THE TGF-b SUPERFAMILY
Siamak Tabibzadeh, Ravi Kothapalli , Ibrahim Buyuksal
Received 7/10/97 Accepted 7/15/97 *: Patent pending
Some human genes such as b-actin and GAPDH mRNAs are present in virtually every cell (1-2). These genes, in view of their abundance, are considered part of the housekeeping gene repertoire. Some other genes are expressed in distinct tissues. For example, thyroglobulin or prostate specific antigen are, respectively, expressed in the thyroid and prostate (3-4). A different set of genes are expressed in cells of distinct lineages. For example, various isoforms of cytokeratin are expressed in the epithelial cells (5-7), vimentin is expressed in the mesenchymal and lymphoid cells (7-11), LCA in the lymphoid cells (12), desmin in the muscle cells (9-11), and neurofilament in the glial cells (9-11). Such a confined gene expression is shared by tumors derived from these tissues allowing the gene product to be used as a tumor marker. Among the most commonly used tumor markers is carcinoembryonic antigen (13). Its serum level is primarily used for the detection of gastrointestinal tumors. The serum level of the CA125 is used in the diagnosis of ovarian tumors and that of prostate specific antigen in the detection of the prostate cancers (4,13). We recently identified a novel member of the TGF-b superfamily, endometrial bleeding associated factor (ebaf), which was expressed in the endometrium (15). According to the guidelines of the Human Gene Nomenclature (http://www.gene.ucl.ac.uk/nomenclature/guidelines.html#Heading6), ebaf has been designated as TGFB4. The expression of the TGFB4 (ebaf) mRNA in endometrium was confined to the late secretory and menstrual phases and was seen in endometria with active bleeding (15). This gene was not expressed in endometrium during proliferative or early or mid-secretory phases of the menstrual cycle (15). In situ hybridization revealed that the gene was expressed primarily in the stroma and rarely in the endometrial glands. Endothelial cells failed to express the gene (15). The expression of the lefty, the mouse homolog of the TGFB4 (ebaf), also showed a narrow tissue-specific distribution. Meng et al, by in situ hybridization showed that the expression of lefty was found only in the mesenchymal cells of the mouse embryo on the left side of the body (16). The expression of lefty disappeared shortly after birth (16). These findings show that the expression of this gene is exquisitely controlled in the body, both in the mouse and in the human. Therefore, to gain an insight on the tissue distribution of the TGFB4 (ebaf) mRNA, in this study, we carried out Northern blot analysis on a panel of normal human tissues. In addition, we also examined the TGFB4 (ebaf) mRNA expression in tumors derived from epithelia, melanocytes and mesenchyme including adenocarcinomas, squamous cell carcinomas, melanomas, lymphomas and various types of sarcomas.