Alternative titles; symbols
HGNC Approved Gene Symbol: SERPINB3
Cytogenetic location: 18q21.33 Genomic coordinates (GRCh38): 18:63,655,197-63,661,893 (from NCBI)
Squamous cell carcinoma antigen (SCCA) is a member of the ovalbumin family of serine proteinase inhibitors. The protein was isolated from a metastatic cervical squamous cell carcinoma by Kato and Torigoe (1977). SCCA is detected in the superficial and intermediate layers of normal squamous epithelium, whereas the mRNA is detected in the basal and subbasal levels. The clinical import of SCCA has been as a circulating tumor marker for squamous cell carcinoma, especially those of the cervix, head and neck, lung, and esophagus. Many clinical studies of cervical squamous cell carcinoma show that the percentage of patients with elevated circulating levels of SCCA increases from approximately 12% at stage 0 to more than 90% at stage IV. Levels fall after tumor resection and rise in approximately 90% of the patients with recurrent disease. Similar trends occur in the other types of squamous cell carcinoma, with a maximum sensitivity of approximately 60% for lung, 50% for esophageal, and 55% for head and neck tumors. The neutral form of SCCA (SCCA1, or SERPINB3) is detected in the cytoplasm of normal and some malignant squamous cells, whereas the acidic form (SCCA2, or SERPINB4; 600518) is expressed primarily in malignant cells and is the major form found in the plasma of cancer patients. Thus, the appearance of the acidic fraction of SCCA is correlated with more aggressive tumors (summary by Schneider et al., 1995).
Suminami et al. (1991) cloned the cDNA for SCCA. The deduced protein contains 390 amino acids and belongs to the serine protease inhibitor family. Northern blot analysis detected a transcript of about 1.7 kb in human squamous cells.
Based on the predicted pI values and molecular masses of SCCA1 and SCCA2, Schneider et al. (1995) suggested that the neutral and acidic forms of SCCA are encoded by SCCA1 and SCCA2, respectively. SCCA1 shares 92% amino acid identity with SCCA2.
Ray et al. (2005) stated that mouse Scca2, or Serpinb3a, exhibits the cysteine-like serine protease inhibitory function of human SCCA1 and the trypsin-like serine protease inhibitory function of human SCCA2. Thus, Scca2 is the mouse ortholog of both human SCCA1 and SCCA2. Ray et al. (2005) found that challenge of uteroglobin (UGB, or SCGB1A1; 192020)-knockout mice with the allergen chicken ovalbumin (OVA) resulted in elevated lung expression of Scca2, as well as elevated levels of the cytokines Il4 (147780) and Il13 (147683) in lung and exacerbated airway inflammation. These effects were countered by reintroduction of recombinant Ugb. Treatment of cultured human bronchial epithelial cells with IL4 or IL13 stimulated SCCA1 and SCCA2 expression via phosphorylation of the transcription factors STAT1 (600555) and STAT6 (601512). SCCA1 and SCCA2 expression was not upregulated by IL4 or IL13 in the presence of an inhibitor of tyrosine phosphorylation. Ray et al. (2005) proposed that UGB controls allergic asthma by downregulating signaling through IL4 and IL13 and inhibiting SCCA1 and SCCA2 expression.
By fluorescence in situ hybridization, Kuwano et al. (1995) mapped the SCCA1 gene to chromosome 18q21. They noted that the PLANH2 gene (173390), with which the SCCA1 gene shares much homology, also maps to chromosome 18q21. The oncogene BCL2 (151430), which is located 600 kb centromeric to PLAH2, is also located on chromosome 18q21.
Schneider et al. (1995) found that SCCA1 and SCCA2 are tandemly arrayed on chromosome 18q21.3 and are flanked by 2 members of the ovalbumin family of serine proteinase inhibitors, plasminogen activator inhibitor type-2 (SERPINB2; 173390) and maspin (SERPINB5; 154790).
Kato, H., Torigoe, T. Radioimmunoassay for tumor antigen of human cervical squamous cell carcinoma. Cancer 40: 1621-1628, 1977. [PubMed: 332328] [Full Text: https://doi.org/10.1002/1097-0142(197710)40:4<1621::aid-cncr2820400435>3.0.co;2-i]
Kuwano, A., Kondo, I., Kishi, F., Suminami, Y., Kato, H. Assignment of the squamous cell carcinoma antigen locus (SCC) to 18q21 by in situ hybridization. Genomics 30: 626, 1995. [PubMed: 8825656] [Full Text: https://doi.org/10.1006/geno.1995.1290]
Ray, R., Choi, M., Zhang, Z., Silverman, G. A., Askew, D., Mukherjee, A. B. Uteroglobin suppresses SCCA gene expression associated with allergic asthma. J. Biol. Chem. 280: 9761-9764, 2005. [PubMed: 15677460] [Full Text: https://doi.org/10.1074/jbc.C400581200]
Schneider, S. S., Schick, C., Fish, K. E., Miller, E., Pena, J. C., Treter, S. D., Hui, S. M., Silverman, G. A. A serine proteinase inhibitor locus at 18q21.3 contains a tandem duplication of the human squamous cell carcinoma antigen gene. Proc. Nat. Acad. Sci. 92: 3147-3151, 1995. [PubMed: 7724531] [Full Text: https://doi.org/10.1073/pnas.92.8.3147]
Suminami, Y., Kishi, F., Sekiguchi, K., Kato, H. Squamous cell carcinoma antigen is a new member of the serine protease inhibitors. Biochem. Biophys. Res. Commun. 181: 51-58, 1991. [PubMed: 1958219] [Full Text: https://doi.org/10.1016/s0006-291x(05)81380-4]