Abstract
Transforming growth factors beta (TGF-β) constitute a family of polypeptide growth factors that control cell growth, cell differentiation and migration, as well as the formation of the extracellular matrix. Recent analyses revealed the overexpression of TGF-β1 in human gastric cancers and demonstrated increased cell proliferation in the stomach of patients with gastric cancer and their first-degree relatives. Using human gastric tissues obtained from patients with gastric cancer (n = 19), biopsies from healthy first-degree relatives of gastric cancer patients (n = 18) and healthy individuals (n = 19), we analysed the expression of TGF-β1 using the reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. Fifteen of 19 patients with gastric cancer expressed TGF-β1 in the tumour. In 11 of these 15 cases TGF-β1 mRNA was also detectable in the non-tumourous stomach. Interestingly, all but two individuals with a first-degree relative diagnosed with gastric cancer exhibited TGF-β1 expression in either the antrum or corpus biopsy or both. In contrast, only one of 19 individuals without a family history of gastric cancer expressed TGF-β1 in the stomach (P< 0.0001). TGF-β1 expression is detectable in a large proportion of gastric cancers and in the stomach of healthy first-degree relatives of gastric cancer patients. Since individuals without gastric cancers in their family express TGF-β1 only in one of 19 cases, the induction of TGF-β1 expression in first-degree relatives of patients with gastric cancer points to the presence of specific molecular alterations in a subgroup of individuals with an increased risk of developing gastric cancer that may precede the development of gastric cancers. © 2000 Cancer Research Campaign
Similar content being viewed by others
Article PDF
Change history
16 November 2011
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
References
Boeing H, Frentzel-Beyme R, Berger M, Berndt V, Göres W, Körner M, Lohmeier R, Menarcher A, Männl HFK, Müller R, Ostermeier H, Paul F, Schwemmle K, Wagner KH and Wahrendorf J (1991) Case–control study on stomach cancer in Germany. Int J Cancer 47: 858–864
Correa P (1992) Human gastric carcinogenesis: a multistep and multifactorial process – first American Cancer Society Award Lecture on cancer epidemiology and prevention. Cancer Res 52: 6735–6740
Delchier JC, Ebert M and Malfertheiner P (1998) Helicobacter pylori in gastric lymphoma and carcinoma. Curr Opin Gastroenterol 14: S41–S45
Ebert M, Yokoyama M, Kobrin MS, Friess H, Lopez ME, Büchler MW and Korc M (1994) Induction and expression of amphiregulin in human pancreatic cancer. Cancer Res 54: 3959–3962
Ebert M, Yokoyama M, Friess H, Kobrin MS, Büchler M and Korc M (1995) Induction of platelet-derived growth factor A and B chains and overexpression of their receptors in human pancreatic cancer. Int J Cancer 62: 529–535
Friess H, Yamanaka Y, Büchler MW, Ebert M, Beger HG, Gold LI and Korc M (1993) Enhanced expression of transforming growth factor β isoforms in pancreatic cancer correlates with decreased survival. Gastroenterology 105: 1846–1856
Fuchs CS and Mayer RJ (1995) Gastric carcinoma. N Engl J Med 333: 32–41
Kingsley D (1994) The TGF-β superfamily: new members, new receptors and new genetic tests of function in different organisms. Genes Dev 8: 133–146
La Vecchia C, Negri E, Franceschi S and Gentile A (1992) Family history and the risk of stomach and colorectal cancer. Cancer 70: 50–55
Macklin MT (1960) Inheritance of cancer of the stomach and large intestine in man. J Natl Cancer Inst 24: 551–571
Mahara K, Kato J, Terui T, Takimoto R, Horimoto M, Murakami T, Mogi Y, Watanabe N, Kongo Y and Nutsu Y (1994) Transforming growth factor beta 1 secreted from scirrhous gastric cancer cells is associated with excess collagen deposition in the tissue. Br J Cancer 69: 777–783
Massague J, Cheifetz S, Laiho M, Ralph DA, Weis FMB and Zentella A (1992) Transforming growth factor-β. Cancer Surv 12: 81–103
Meining A, Hackelsberger A, Daenecke C, Stolte M, Bayerdörffer E and Ochsenkühn T (1998) Increased cell proliferation of the gastric mucosa in first degree relatives of gastric carcinoma patients. Cancer 83: 876–881
Miehlke S, Hackelsberger A, Meining A, Hatz R, Lehn N, Stolte M and Bayerdörffer E (1997) Severe expression of corpus gastritis is characteristic in gastric cancer patients infected with Helicobacter pylori. Int J Cancer 73: 837–839
Muso E, Yoshida H, Takeuchi E, Yashiro M, Matsushima H, Oyama A, Suyama K, Kawamura T, Kamata T, Miyawaki S, Izui S and Sasayama S (1996) Enhanced production of glomerular extracellular matrix in a new mouse strain of high serum IgA ddY mice. Kidney Int 50: 1946–1957
Naef M, Ishiwata T, Friess H, Büchler MW, Gold LI and Korc M (1997) Differential localization of transforming growth factor-β isoforms in human gastric mucosa and overexpression in gastric carcinoma. Int J Cancer 71: 131–137
Nakamura M, Katano M, Kuwahara A, Fujimoto K, Miyazaki K, Morisaki T and Mori M (1998) Transforming growth factor β1 (TGF-β1) is a preoperative prognostic indicator in advanced gastric carcinoma. Br J Cancer 78: 1373–1378
Nakatsuru S, Yanagisawa A, Furukawa Y, Ichii S, Kato Y, Nakamura Y and Horii A (1993) Somatic mutations of the APC gene in precancerous lesions of the stomach. Hum Mol Genet 2: 1463–1465
Ottini L, Palli D, Falchetti M, Dámico C, Amorosi A, Saieva C, Calzolari A, Cimoli F, Tatarelli C, De Marchis L, Masala G, Mariani-Costantini R and Cama A (1997) Microsatellite instability in gastric cancer is associated with tumor location and family history in a high-risk population from Tuscany. Cancer Res 57: 4523–4529
Price AB (1991) The Sydney system: histological division. J Gastroenterol Hepatol 6: 209–222
Siegel S (1956). Non-parametric Statistics for Behavorial Sciences, McGraw-Hill: New York
Scott N, Landsdown M, Diament R, Rathbone B, Murday V, Wyatt JI, McMahou M, Dixon M and Quirke P (1990) Helicobacter gastritis and intestinal metaplasia in a gastric cancer family. Lancet 335: 728
Soman NR, Wogan GN and Rhim JS (1990) TPR-MET oncogenic rearrangement: detection by polymerase chain reaction amplification of the transcript and expression in human tumor cell lines. Proc Natl Acad Sci USA 87: 738–742
Tahara E, Semba M and Tahara H (1996) Molecular biological observations in gastric cancer. Semin Oncol 23: 307–315
Wright PA, Quirke P, Attanoos R and Williams GT (1992) Molecular pathology of gastric carcinoma: progress and prospects. Hum Pathol 23: 848–859
Author information
Authors and Affiliations
Rights and permissions
From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Ebert, M., Yu, J., Miehlke, S. et al. Expression of transforming growth factor beta-1 in gastric cancer and in the gastric mucosa of first-degree relatives of patients with gastric cancer. Br J Cancer 82, 1795–1800 (2000). https://doi.org/10.1054/bjoc.1999.1107
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1054/bjoc.1999.1107
Keywords
This article is cited by
-
Influence of TGFB1 C-509T polymorphism on gastric cancer risk associated with TGF-β1 expression in the gastric mucosa
Gastric Cancer (2015)
-
An updated meta-analysis of transforming growth factor-β1 gene: three polymorphisms with gastric cancer
Tumor Biology (2014)
-
Relation between transforming growth factor-β1 expression, its receptor and clinicopathological factors and survival in HER2-negative gastric cancers
Wiener klinische Wochenschrift (2011)
-
TGFB1 gene polymorphisms: their relevance in the susceptibility to Helicobacter pylori-related diseases
Genes & Immunity (2006)
-
Increased expression of survivin in gastric cancer patients and in first degree relatives
British Journal of Cancer (2002)