A serine proteinase inhibitor locus at 18q21.3 contains a tandem duplication of the human squamous cell carcinoma antigen gene.

Schneider, Sandra; Schick, Charles; Fish, Kimberlee E.; Miller, Eric S.; Pena, Jeannette C.; Treter, S.; Hui, Stephanie M.; Silverman, Gary A.

doi:10.1073/pnas.92.8.3147

Cited by 259 publications

(210 citation statements)

References 31 publications

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“…The neutral and acidic isoforms of SCCA are encoded by 2 separate, but highly homologous genes, SCCA1 and SCCA2, at chromosome 18q21.3 [6]. Although SCCA1 and SCCA2 are with 91% identity at the amino acid concentration, they have distinct properties and substrate specificities.…”

Section: Abstract: Hepatocellular Carcinoma Liver Diseases Prognosmentioning

confidence: 99%

Squamous cell carcinoma antigen 1 and 2 mRNA and a new variant expressed in hepatocellular carcinoma

LI¹,

Gao²,

Yang³

et al. 2014

neo

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New tools for diagnostic of HCC remain to further investigate. We have evaluated the expression of SCCA1, 2 mRNA and their prognostic value in hepatocellular carcinoma (HCC).Reverse transcription polymerase chain reaction (RT-PCR) and direct sequencing were performed to evaluate the mRNA expression of SCCA1 and SCCA2 in 93 HCCs, and 93 paired adjacent non-cancerous tissues (PNT), 16 cirrhosis livers and 9 normal livers. The correlation of SCCA variants expression with the clinical parameters and the factors affecting survival were analyzed statistically.Total SCCA was detected in 33.3% of HCCs (31/93), in 9.68% of PNT (9/93) and 22.2% of normal livers (2/9). No expression was found in cirrhosis livers (0/16). The frequencies of total SCCA expression were significantly higher in HCCs than that in PNT and liver cirrhosis (p = 0.000, 0.006). From mRNA sequencing of HCCs, a new SCCA1 variant (presenting a T357A mutation) was identified in 16 specimens, while wild type SCCA1 was identified in 11 specimens and SCCA2 in 27 specimens. Clinicopathological analysis showed that the frequency of SCCA1 was significantly higher in poorly differentiated HCC, compared with moderately and well differentiated tumors (p = 0.021). T357A variant has a significantly higher frequency in nonencapsulated tumors than wild type SCCA1 (p = 0.034).The SCCA1, 2 mRNA is effective for detecting HCC and could be potentially applied in HCC diagnosis. Key words: hepatocellular carcinoma, liver diseases, prognosis, squamous cell carcinoma antigenNeoplasma 61, 6, 2014 doi:10.4149/neo_2014_087 Liver cancer is the fifth most frequently diagnosed cancer but the second most frequent cause of cancer death in men worldwide (half of these cases and deaths are estimated to occur in China), and approximately, 70-85% of the total liver cancer are classified as hepatocellular carcinoma (HCC) [1]. Early detection enables us to provide the patients with more therapeutic options, which can improve survival rate of patients and reduce medical costs [2]. Despite the fact that serum AFP is still the golden standard amongst diagnostic markers for HCC, its diagnostic value is more and more questioned, because of its poor sensitivity and specificity [3,4]. Therefore, investigators are seeking for better HCC biomarkers.Squamous cell carcinoma antigen (SCCA), originally isolated from SCC tissue of the uterine cervix, is a member of the family of serine protease inhibitors [5]. The neutral and acidic isoforms of SCCA are encoded by 2 separate, but highly homologous genes, SCCA1 and SCCA2, at chromosome 18q21.3 [6]. Although SCCA1 and SCCA2 are with 91% identity at the amino acid concentration, they have distinct properties and substrate specificities. SCCA1 also known as SERPINB3, a papain-like cysteine proteinase inhibitor, inhibits cathepsins K, L and S [7]. SCCA2 also known as SERPINB4, a chymotrypsin-like serine proteinase inhibitor, inhibits proteolytic activity of endogenous cathepsin G and mast cell chymase [8]. The biological role of this serpin in carcinoge...

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Section: Abstract: Hepatocellular Carcinoma Liver Diseases Prognosmentioning

confidence: 99%

Squamous cell carcinoma antigen 1 and 2 mRNA and a new variant expressed in hepatocellular carcinoma

LI¹,

Gao²,

Yang³

et al. 2014

neo

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“…12 Further cloning of the genomic region of chromosome 18q21.3 revealed two tandemly arrayed SCCA genes, designated SCCA1 and SCCA2. 13 Although SCCA1 and SCCA2 are nearly identical, they differ in their reactive site loop and exhibit different functions. SCCA1 inhibits the papain-like cysteine proteinases cathepsin S, K, and L, whereas SCCA2 inhibits the chymotrypsin-like serine proteinases cathepsin G and mast cell chymase.…”

Section: Introductionmentioning

confidence: 99%

Conditionally replicating E1B-deleted adenovirus driven by the squamous cell carcinoma antigen 2 promoter for uterine cervical cancer therapy

Hsu

Huang

et al. 2008

Cancer Gene Ther

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Cervical cancer is the second most common type of malignant tumor among women worldwide. When the disease is confined locally, it can be controlled with surgical resection and radiotherapy. However, patients with recurrent or metastatic disease often have a poor prognosis. Measurement of serum levels of squamous cell carcinoma (SCC) antigens has been widely used as serological markers for SCC of uterine cervix. Recently, it has been demonstrated that cervical cancer patients with elevated squamous cell carcinoma antigen-2 (SCCA2) expression in tumor cells carry a poor prognosis. Here, by using a luciferase reporter assay, we show that SCCA2 promoter was active in SCCA2-producing human cervical cancer cell lines, including Cx, Cxwj, SiHa and HeLa cells, but relatively quiescent in normal cervical epithelial cells. We then developed a conditionally replicating adenovirus, designated Ad-KFH, under the transcriptional control of the SCCA2 promoter. This E1B-55 kDa-deleted oncolytic adenovirus replicated specifically in and lysed SCCA2-producing cervical cancer cells. Furthermore, in a peritoneal metastatic tumor model, Ad-KFH retarded Cxwj tumor growth in NOD/severe combined immunodeficient mice and prolonged survival of tumor-bearing mice, especially when combined with cisplatin. These results suggest that Ad-KFH may provide a new strategy of gene therapy for advanced or recurrent uterine cervical cancer.

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“…Interestingly, although their amino-acid sequences also indicate that SCCA1 and SCCA2 share 92% identical residues overall with predicted identical secondary structures, 13 structural and functional analyses of the recombinant proteins show that SCCA1 encodes a papain-like cysteine proteinase inhibitor comprising the neutral SCCA fractions, whereas SCCA2 encodes a chymotrypsin-like serine proteinase inhibitor comprising the acidic fractions. 13,14 Non-cancerous squamous epithelia mostly expresses the neutral fraction encoded by the SCCA1 gene, whereas SCC tissues contain both acidic and neutral SCCA fractions. 15 Quantitative analyses have also shown that SCCA1 mRNA did not show significant differences between SCC and normal tissues, 14 while high expression of SCCA2 mRNA was seen in SCC tissues but not in normal tissues 14 and was associated with a poor prognosis in SCC of the head and neck.…”

Section: Introductionmentioning

confidence: 99%

“…12 Molecular cloning of the SCCA locus in the human genome has revealed the presence of two tandem arrayed genes, SCCA1 and SCCA2, that are 95% identical in cDNA nucleotide sequence. Interestingly, although their amino-acid sequences also indicate that SCCA1 and SCCA2 share 92% identical residues overall with predicted identical secondary structures, 13 structural and functional analyses of the recombinant proteins show that SCCA1 encodes a papain-like cysteine proteinase inhibitor comprising the neutral SCCA fractions, whereas SCCA2 encodes a chymotrypsin-like serine proteinase inhibitor comprising the acidic fractions. 13,14 Non-cancerous squamous epithelia mostly expresses the neutral fraction encoded by the SCCA1 gene, whereas SCC tissues contain both acidic and neutral SCCA fractions.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional targeting of adenovirus vectors with the squamous cell carcinoma-specific antigen-2 promoter for selective apoptosis induction in lung cancer

et al. 2006

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Squamous cell carcinoma antigens SCCA1 and SCCA2 are highly homologous serine proteinase inhibitors which have been widely utilized as serological markers for squamous cell cancers, but it has recently been demonstrated that only SCCA2 is truly specific for certain forms of lung cancer. Using a construct containing the 5 0 -flanking region of the SCCA2 gene between À460 and þ 0 bp and the luciferase reporter gene, SCCA2 promoter activity was detected in SCCA2-producing SCC cell lines (LK-2, LC-1), but not in SCCA2-nonproducing lung adenocarcinoma cell lines (A549, ABC-1, and RERF-LC-MS) or normal cells (WI-38, SAEC, and NHEKAdult). Infection with a recombinant adenovirus vector, Ad-SCCA2-DsRed, resulted in cell-specific expression of the SCCA2 promoter-driven DsRed marker gene only in LK-2 and LC-1 cells. The same strategy was used for SCCA2-driven expression of a proapoptotic gene, (KLAKLAK)2, which can cause mitochondrial disruption by triggering mitochondrial permeabilization and swelling, resulting in the release of cytochrome c and induction of apoptosis. Infection with Ad-SCCA2-KLAKLAK2 specifically reduced the growth of the two human lung SCC cell lines compared to the SCCA2 nonproducing cell lines both in vitro and in vivo, suggesting that the SCCA2 promoter had a tumor-specific effect. These results suggest that transduction of SCCA2 promotercontrolled suicide genes by adenoviral vectors can confer transcriptionally targeted cytotoxicity in SCCA2-producing lung SCC cells, and represents a novel strategy for gene transfer specifically targeted to SCC in the lung. Cancer Gene Therapy ( IntroductionLung carcinoma is the most common malignant neoplasm and represents the leading cause of cancer death in the developed world. 1 Among lung carcinomas, adenocarcinoma and squamous cell carcinoma (SCC) are the most frequently encountered forms. Despite the use of optimal chemotherapy and radiotherapy regimens, there has been little improvement in the prognosis of these cancer patients during the last decade. 2,3 This underscores the need to seek novel therapeutic modalities for lung cancer patients. One such approach is gene therapy by administration of vectors expressing cytotoxic genes; however, in order to maximize tumor-killing efficacy and minimize any potential adverse effects of this approach, it would be advantageous to employ a cancer-specific targeting strategy. For adenocarcinomas in general, transcriptional targeting by the use of cancer-specific promoters such as the carcinoembryonic antigen (CEA) promoter has been described previously. 4,5 However, little has been reported for SCC-specific regulation.The squamous cell carcinoma antigen (SCCA) was first reported by Kato et al. 6 in 1977 as a circulating tumor marker for SCC, particularly that of cervix, head and neck, esophagus, and lung. 7 Several studies have shown that increased serum SCCA levels are seen in SCC patients 8,9 and correlate with the extent of disease in patients with SCC, 10,11 although the protein itself is not detected in adenoca...

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A serine proteinase inhibitor locus at 18q21.3 contains a tandem duplication of the human squamous cell carcinoma antigen gene.

Abstract: The squamous cell carcinoma antigen (SCCA) is a member of the ovalbumin family of serine proteinase

Cited by 259 publications

References 31 publications

Squamous cell carcinoma antigen 1 and 2 mRNA and a new variant expressed in hepatocellular carcinoma

Squamous cell carcinoma antigen 1 and 2 mRNA and a new variant expressed in hepatocellular carcinoma

Conditionally replicating E1B-deleted adenovirus driven by the squamous cell carcinoma antigen 2 promoter for uterine cervical cancer therapy

Transcriptional targeting of adenovirus vectors with the squamous cell carcinoma-specific antigen-2 promoter for selective apoptosis induction in lung cancer

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A serine proteinase inhibitor locus at 18q21.3 contains a tandem duplication of the human squamous cell carcinoma antigen gene.

Abstract: The squamous cell carcinoma antigen (SCCA) is a member of the ovalbumin family of serine proteinase

Cited by 259 publications

References 31 publications

Squamous cell carcinoma antigen 1 and 2 mRNA and a new variant expressed in hepatocellular carcinoma

Squamous cell carcinoma antigen 1 and 2 mRNA and a new variant expressed in hepatocellular carcinoma

Conditionally replicating E1B-deleted adenovirus driven by the squamous cell carcinoma antigen 2 promoter for uterine cervical cancer therapy

Transcriptional targeting of adenovirus vectors with the squamous cell carcinoma-specific antigen-2 promoter for selective apoptosis induction in lung cancer

Contact Info

Product

Resources

About

Squamous cell carcinoma antigen 1 and 2 mRNA and a new variant expressed in hepatocellular carcinoma

Squamous cell carcinoma antigen 1 and 2 mRNA and a new variant expressed in hepatocellular carcinoma