BackgroundThe transforming growth factors (TGF)-β, TGF-β1, TGF-β2 and TGF-β3, and their receptors [TβRI, TβRII, TβRIII (betaglycan)] elicit pleiotropic functions in the prostate. Although expression of the ligands and receptors have been investigated, the splice variants have never been analyzed. We therefore have analyzed all ligands, the receptors and the splice variants TβRIB, TβRIIB and TGF-β2B in human prostatic cells.ResultsInterestingly, a novel human receptor transcript TβRIIC was identified, encoding additional 36 amino acids in the extracellular domain, that is expressed in the prostatic cancer cells PC-3, stromal hPCPs, and other human tissues. Furthermore, the receptor variant TβRIB with four additional amino acids was identified also in human. Expression of the variant TβRIIB was found in all prostate cell lines studied with a preferential localization in epithelial cells in some human prostatic glands. Similarly, we observed localization of TβRIIC and TGF-β2B mainly in the epithelial cells with a preferential localization of TGF-β2B in the apical cell compartment. Whereas in the androgen-independent hPCPs and PC-3 cells all TGF-β ligands and receptors are expressed, the androgen-dependent LNCaP cells failed to express all ligands. Additionally, stimulation of PC-3 cells with TGF-β2 resulted in a significant and strong increase in secretion of plasminogen activator inhibitor-1 (PAI-1) with a major participation of TβRII.ConclusionIn general, expression of the splice variants was more heterogeneous in contrast to the well-known isoforms. The identification of the splice variants TβRIB and the novel isoform TβRIIC in man clearly contributes to the growing complexity of the TGF-β family.

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The transforming growth factors (TGF)-beta, TGF-beta1, TGF-beta2, and TGF-beta3, and their receptors [TbetaRI, TbetaRII, TbetaRIII (betaglycan)] elicit many functions in the testis, for example, they perturb the blood testis barrier (BTB). Although expression of the ligands and receptors have been investigated, the alternative splice variants are incompletely examined. We therefore have analyzed all ligands, the receptors, and the splice variants TbetaRIB, TbetaRIIB, and TGF-beta2B in testicular cells from rat and mouse. In mouse, the novel transcript variant TGF-beta2B was identified and was found in Leydig cells, spermatogonia, pachytene spermatocytes, and in the apical regions of the Sertoli cells in adult testis. Even though expression of the splice variant TbetaRIB could be shown in mouse and rat, we never found the isoform TbetaRIIB in the rat cell lines studied. Whereas in all testicular cells expression of all TGF-beta ligands could be shown, receptor mRNA expression was slightly more diverse. Furthermore, expression pattern of the splice variants was more heterogeneous, for example, TbetaRIB was not detectable in adult Sertoli cells, primary peritubular cells, and immortalized peritubular cells. The heterogeneous expression of the receptors and especially of the splice variants might provide possible clues for the different functions of the TGF-beta ligands in testicular cells.

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