The primary structure of the human pancreatic secretory trypsin inhibitor

Bartelt, Diana C.; Shapanka, Roslyn; Greene, Lewis J.

doi:10.1016/0003-9861(77)90103-5

Cited by 104 publications

(50 citation statements)

References 33 publications

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“…They share ∼50% amino acid sequence homology (21,22) and have similar numbers of amino acid residues (56 and 53, respectively; molecular weights ∼6 kDa) and three intrachain disulfide bridges (21)(22)(23). In addition, SPINK1 has been shown to bind specifically to several cell lines (24), suggesting that SPINK1 works as a growth factor in tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Serine Protease Inhibitor Kazal Type 1 Promotes Proliferation of Pancreatic Cancer Cells through the Epidermal Growth Factor Receptor

Ozaki

Ohmuraya

Hirota

et al. 2009

Molecular Cancer Research

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Serine protease inhibitor, Kazal type 1 (SPINK1) is expressed not only in normal human pancreatic acinar cells but also in a variety of pancreatic ductal neoplasms. There are structural similarities between SPINK1 and epidermal growth factor (EGF). Hence, we hypothesized that SPINK1 binds to EGF receptor (EGFR) to activate its downstream signaling. We first showed that SPINK1 induced proliferation of NIH 3T3 cells and pancreatic cancer cell lines. We showed that SPINK1 coprecipitated with EGFR in an immunoprecipitation experiment and that the binding affinity of SPINK1 to EGFR was about half of that of EGF using quartz-crystal microbalance (QCM) technique. As expected, EGFR and its downstream molecules, signal transducer and activator of transcription 3, v-Akt murine thymoma viral oncogene homologue, and extracellular signal-regulated kinase 1/2, were phosphorylated by SPINK1 as well as EGF. To determine which pathway is the most important for cell growth, we further analyzed the effect of inhibitors. Growth stimulation by EGF or SPINK1 was completely inhibited by EGFR and mitogen-activated protein kinase/ extracellular signal-regulated kinase kinase inhibitor but not by Janus-activated kinase and phosphoinositide 3-kinase inhibitors. To further analyze the clinical importance of SPINK1 in the development of pancreatic cancer, we examined the expression of SPINK1 and EGFR in pancreatic tubular adenocarcinomas and pancreatic intraepithelial neoplasm. Both SPNK1 and EGFR were coexpressed not only in the early stage of cancer, PanIN-1A, but also in advanced stages. Taken together, these results suggest that SPINK1 stimulates the proliferation of pancreatic cancer cells through the EGFR/mitogen-activated protein kinase cascade. (Mol Cancer Res 2009;7(9):1572-81)

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Section: Introductionmentioning

confidence: 99%

Serine Protease Inhibitor Kazal Type 1 Promotes Proliferation of Pancreatic Cancer Cells through the Epidermal Growth Factor Receptor

Ozaki

Ohmuraya

Hirota

et al. 2009

Molecular Cancer Research

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“…TATI levels are also elevated in patients with pancreatitis and severe pneumonia (Huhtala et al, 1983). Determination of the N-terminal amino acid sequence of TATI has revealed that it is closely related or identical to the pancreatic secretory trypsin inhibitor (PSTI) (Kazal et al, 1948;Bartelt et al, 1977;Huhtala et al, 1982). Elevated levels of PSTI have been found in serum and urine of patients with pancreatitis (Eddeland & Ohlsson, 1978;Kitahara et al, 1980;Ogawa et al, 1980), and in serum of patients both with pancreatic cancer and various other malignancies Murata et al, 1983).…”

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confidence: 99%

Tumour-associated trypsin inhibitor, TATI, in patients with pancreatic cancer, pancreatitis and benign biliary diseases

Haglund¹,

Huhtala²,

Halila³

et al. 1986

Br J Cancer

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Summary The serum and urine concentrations of a tumour-associated trypsin inhibitor, TATI, were determined by radioimmunoassay in patients with pancreatic cancer and with benign pancreatic and biliary diseases. Elevated serum levels (>20 pug1-1) were found in 85% of the patients with pancreatic cancer, and elevated urine levels (>50pgg-1 creatinine) in 96% of the patients. Immunohistochemical staining of pancreatic lesions showed that half of the pancreatic tumours expressed TATI, but the pancreatic tissue adjacent to a carcinoma always stained stronger than the carcinoma. It therefore seems that the main source of TATI in serum and urine of patients with pancreatic cancer are the normal acini and not the tumour tissue. In pancreatitis the staining was intense and clearly stronger than in normal pancreas.The tumour-associated trypsin inhibitor, TATI, is a 6000 dalton peptide, isolated from the urine of a patient with ovarian cancer Huhtala et al., 1982). Elevated concentrations have been found in the urine of patients with gynaecological cancer, in amniotic fluid and in some extracts from malignant tumours . TATI levels are also elevated in patients with pancreatitis and severe pneumonia (Huhtala et al., 1983 Murata et al., 1983). Immunohistochemically PSTI has been demonstrated in normal acinar cells, but could not be detected in tissue specimens of pancreatic cancer (Marks et al., 1984).In the present work that TATI levels in serum

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“…Immediately adjacent to the N terminal domain is a stretch of 30-45 amino acid residues that has 30% similarity to the Kazal family of serine proteinase inhibitors, including the human pancreatic secretory trypsin inhibitor [38]. This domain, known as a KI domain, is also found in follistatin, leading to the hypothesis that IGFBP7 was a follistatin-like protein [35].…”

Section: Igfbp7 Overviewmentioning

confidence: 99%