Disease relevance of SERPINB4

• Further characterization of the region should determine whether the differential expression of the SCCA genes plays a causal role in development of more aggressive squamous cell carcinomas [1].
• We have assessed whether squamous cell carcinoma antigen (SCCA), a serpin overexpressed in neoplastic cells of epithelial origin, is also expressed in liver cancer [2].
• The transcriptional activity of SCCA1 promoter was up-regulated in squamous cell carcinoma cells, compared with keratinocyte and adenocarcinoma cells [3].
• The cDNA was expressed in Escherichia coli and the product was detected using Western blotting with antibodies against SCCA [4].
• Relative levels of SCCA2 and SCCA1 mRNA in primary tumors predicts recurrent disease in squamous cell cancer of the head and neck [5].

High impact information on SERPINB4

• We initially found significantly elevated levels of IP-10 in freshly isolated human NSCLC samples of squamous cell carcinoma (SCCA) [6].
• UV-induced apoptosis was significantly decreased when SCCA was overexpressed in 3T3/J2 cells [7].
• Upon exposure of keratinocytes to UV, SCCA1 was bound to JNK1 and transferred to the nucleus [7].
• Involucrin promoter-driven SCCA1 transgenic mice showed remarkable resistance against UV irradiation [7].
• The reactive site loop of the serpin SCCA1 is essential for cysteine proteinase inhibition [8].

Chemical compound and disease context of SERPINB4

• Squamous cell carcinoma antigen (SCCA) is a member of the ovalbumin serine protease inhibitor family, and the serum level of SCCA is a tumor marker of squamous cell carcinoma [4].
• Quantitative RT-PCR ELISA digoxigenin-labeling assay demonstrated that SCCA1 mRNA expression in squamous cell carcinoma cell lines was respectively 2.8 times and 42 times that in keratinocyte and non-squamous cell carcinoma cell lines [9].
• BACKGROUND AND PURPOSE: Thallium-201 single-photon emission computed tomography (SPECT) can be used to detect primary squamous cell carcinoma (SCCA) of the head and neck [10].
• BACKGROUND AND PURPOSE: The choline (Cho)/creatine (Cr) ratio has been shown to be a reliable proton MR spectroscopy metabolic marker for differentiating squamous cell carcinoma (SCCA) from normal muscle in the upper aerodigestive tract [11].

Biological context of SERPINB4

• The predicted amino acid sequences were 92% identical and suggested that the neutral form of the protein was encoded by SCCA1 and the acidic form was encoded by SCCA2 [1].
• Although SCCA1 and SCCA2 are nearly identical in primary structure, the reactive site loop of each inhibitor suggests that they may differ in their specificity for target proteinases [12].
• Uteroglobin suppresses SCCA gene expression associated with allergic asthma [13].
• When the fact that mammals and birds diverged approximately 310 million years ago is considered, an ancestral SCCA/SQN-like serpin with dual inhibitory activity may be present in many mammalian genomes [14].
• Aberrant expression of serpin squamous cell carcinoma antigen 2 in human tumor tissues and cell lines: evidence of protection from tumor necrosis factor-mediated apoptosis [15].

Anatomical context of SERPINB4

• Two isoforms of SCCA, deriving from 2 highly homologous serine proteinase inhibitor genes, are co-expressed in normal and malignant squamous epithelium, but it is mainly the acidic isoform SCCA2 that is present in the circulation of cancer patients [5].
• Circulating serpin tumor markers SCCA1 and SCCA2 are not actively secreted but reside in the cytosol of squamous carcinoma cells [16].
• Squamous cell carcinoma antigen (SCCA) is widely used as a serum marker in cancers of the uterine cervix, the head and neck, lung and esophagus [5].
• Although SCCA1 and SCCA2 are detected in the cytoplasm of normal squamous epithelial cells, neither serpin is detected normally in the serum [16].
• Using subcellular fractionation, SCCA-green fluorescent fusion protein expression and confocal microscopy, SCCA1 and SCCA2 were found exclusively in the cytosol and were not associated with nuclei, mitochondria, lysosomes, microtubules, actin or the Golgi [16].

Associations of SERPINB4 with chemical compounds

• The squamous cell carcinoma antigen (SCCA) is a member of the ovalbumin family of serine proteinase inhibitors (serpins) [1].
• SCCA1 has been shown to be effective against papain-like cysteine proteinases [12].
• We report here that compared with wild type littermates, UG-KO mouse lungs express markedly elevated levels of SCCA-2 mRNA and protein, which are augmented by allergen-challenge [13].
• Using recombinant DNA techniques, we prepared a fusion protein of glutathione S-transferase and full-length SCCA2 . The recombinant SCCA2 was most effective against two chymotrypsin-like proteinases from inflammatory cells, but was ineffective against papain-like cysteine proteinases [12].
• Simple modifications of the serpin reactive site loop convert SCCA2 into a cysteine proteinase inhibitor: a critical role for the P3' proline in facilitating RSL cleavage [17].

Regulatory relationships of SERPINB4

• Our previous studies show that SCCA2 inhibits chymotrypsin-like serine proteinases [Schick et al. (1997) J. Biol. Chem. 272, 1849-1855] [18].
• SCCA2 inhibited CTSG at 1:1 stoichiometry and with a second-order rate constant of kass = 1.7 x 10(5) M-1 s-1 [19].
• We investigated if the reactive centre loop (RCL) was necessary to allow SCCA2 to inhibit TNF alpha-mediated apoptosis [20].
• In conclusion, SCCA2 regulates cell migration and invasion via E-cadherin expression, suggesting that SCCA2 may be involved in cancer behavior such as invasion or metastasis [21].

Other interactions of SERPINB4

• The squamous cell carcinoma antigen (SCCA) 1 and its homologous molecule, SCCA2, belong to the ovalbumin-serpin family [22].
• These data showed that SCCA2 is a novel inhibitor of two physiologically important chymotrypsin-like serine proteinases [12].
• Recent reports indicate that human orthologs of murine squamous cell carcinoma antigen-2 (SCCA-2/serpinb3a), a serine protease-inhibitor, are overexpressed in the airways of asthmatic patients [13].
• Thus, SCCA2 overexpression in squamous tumor cells contributed to their survival by protecting them against TNF-alpha-induced apoptosis [15].
• In addition, a significant level of SCCA2 mRNA expression was detected in the HSC-4 cell line, but not in Ca9, HeLa, SKG-IIIa, or HSC-3 cells [15].

Analytical, diagnostic and therapeutic context of SERPINB4

• Molecular cloning of the SCCA genomic region revealed the presence of two tandemly arrayed genes, SCCA1 and SCCA2 [12].
• From sequence alignment, a novel SCCA1 variant (G(351) to A) was identified in five cases, while SCCA1 was revealed in six cases and SCCA2 in three cases [2].
• These results suggest that the level of expression of SCCA2 mRNA detected by RT-PCR can be used to evaluate the status of SCC tumors [15].
• RESULTS: Isoelectric focusing shows that leupin is the more acidic antigen with a determined pI for recombinant leupin (rLeupin) of 6.01, with rSCCA having a pI of 6.17 [23].
• In the present study, asymmetric semi-nested reverse transcription PCR, based on the principle of fluorescence energy transfer, enabled to quantitate the copy numbers of both SCCA1 and SCCA2 mRNAs [24].

References