In the present study, we further studied mechanisms of transcriptional regulation of the tumor-associated carbonic anhydrase IX (CAIX). We identified PR5 in the CA9 promoter as another SP1/SP3-binding site. As shown by electromobility shift assays and block-replacement mutagenesis, PR5 is functionally equivalent to the SP1/SP3-binding PR1 identified previously. However, there is a strong requir...

BACKGROUND Expression of the Sp1 transcription factor is induced by hypoxia, and the ADAM17 promoter contains predicted Sp1 binding sites. ADAM17 contributes to hypoxic-induce invasiveness of glioma. In this study, we investigated whether Sp1 transcription factor induces ADAM17 and/or contributes to tumor cell invasiveness in hypoxia. METHODS Employing RT-PCR and Western blot, we examined the...

Sp4 is a human sequence-specific DNA binding protein with structural features similar to those described for the transcription factors Sp1 and Sp3. These three proteins contain two glutamine-rich regions and a highly conserved DNA binding domain composed of three zinc fingers. Consistently, Sp1, Sp3, and Sp4 do have the same DNA binding specificities. In this report, we have embarked on a detai...

Selective transcription of the human CYP2F1 gene in lung tissues may control the susceptibilities of this organ to diverse pneumotoxicants and lung carcinogens. However, the mechanisms responsible for CYP2F1 organ-selective transcription have not been elucidated. The objectives of the current studies were to identify and characterize basal transcription elements within the TATA-less promoter re...

Previous studies have shown that androgen up-regulates expression of the p21 (WAF1, CIP1, SDI1, CAP20) gene, which contains a canonical androgen response element (ARE) in its proximal promoter region. We undertook the current studies to determine whether elements in the p21 promoter other than the ARE mediate androgen action. We found that deletion of the ARE did not completely abolish the prom...

UNLABELLED Multiple lines of evidence implicate over-expression and activation of the androgen receptor (AR) in the progression of prostate cancer (PC) to androgen-independence (AI) and resistance to therapy. The mechanisms leading to AR over-expression are not fully understood but binding of Sp1 to specific Sp1-binding sites in the AR promoter and 5'-untranslated region (5'-UTR) was shown to u...

The impact of antiangiogenic therapy on the Sp1/vascular endothelial growth factor (VEGF) pathway and that of alteration of Sp1 signaling on the efficacy of antiangiogenic therapy is unclear, yet understanding their interactions has significant clinical implications. Treatment with bevacizumab, a neutralizing antibody against VEGF, suppressed human pancreatic cancer growth in nude mice. Gene ex...

The receptor tyrosine kinase c-kit is necessary for normal hematopoiesis, the development of germ cells and melanocytes, and the pathogenesis of certain hematologic and nonhematologic malignancies. To better understand the regulation of the c-kit gene, a detailed analysis of the core promoter was performed. Rapid amplification of cDNA ends (RACE) and RNase protection methods showed two major tr...

Here, we describe a novel member in the group of membrane-anchored chymotrypsin (S1)-like serine proteases, namely testis serine protease 1 (T-SP1), as it is principally expressed in testis tissue. The human T-SP1 gene encompasses 28.7 kb on the short arm of chromosome 8 and consists of seven exons. Rapid amplification of cDNA ends (RACE) experiments revealed that due to alternative splicing th...

Membrane type serine protease 1 (MT-SP1) is a representative member of a large family of related enzymes known as type II transmembrane serine proteases or membrane type serine proteases. MT-SP1 has been implicated in the selective proteolysis of key extracellular substrates but its physiological role is still not fully understood. MT-SP1 expression at the protein and RNA level has been previou...