Abstract
The deleted-in-colorectal-cancer (DCC) gene, located on chromosome 18q 21.3, is considered to be a tumor suppressor gene related to cellular adhesion receptors. A loss of heterozygosity (LOH) on chromosome 18q is frequently observed in adenomatous polyposis coli, as well as in sporadic colon carcinoma and its liver metastatic loci. In this study, we investigated the expression of DCC mRNA in the resected specimens of 38 gastric cancers and 28 colorectal cancers by a reverse transcription-polymerase chain reaction method. In the gastric cancer patients, the mean expression level of DCC mRNA in the tumors was significantly lower than that in normal tissues (P=0.009), but no difference was observed in the colorectal cancer patients. DCC mRNA expression was decreased in 15 gastric cancers (40%) and 10 colorectal cancers (36%), and there was a significant correlation between the decreased expression of DCC mRNA and nodal metastasis in colorectal cancer (x 2=7.049, DF=1, P=0.0079). Two of four gastric cancer patients and none of seven colorectal cancer patients whose cancers were confined to the muscularis propria without metastasis showed decreased expression of DCC mRNA. These findings demonstrate that decreased expression of DCC mRNA may occur at an early stage in gastric cancer and at a late stage in colorectal cancer and that this decreased expression correlates with the potential to develop nodal metastasis.
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Friend SH, Bernards R, Rogeli S, Weinberg RA, Rapaport JM, Albert DM, Dryja TP (1986) A human DNA segment with properties of the gene that predisposed to retinoblastoma and osteosarcoma. Nature 323:643–646
Baker SJ, Fearon ER, Nigro JM, Hamilton SR, Preisinger AC, Jessup JM, Van Tuinen P, Ledbetter DH, Baker D, Nakamura Y, White R, Vogelstein B (1989) Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science 244:217–221
Kinzler KW, Nilbert MC, Su LK, Vogelstein B, Bryan TM, Levy DP, Smith KJ, Preisinger AC, Hedge P, McKechnie D, Finniear R, Markham A, Groffen J, Boguski MS, Altschul SF, Horii A, Ando H, Miyoshi Y, Miki Y, Nishisho I, Nakamura Y (1991) Identification of FAP locus genes from chromosome 5q21. Science 253:661–665
Groden J, Thliveris A, Samowitz W, Carlson M, Gelbert L, Albertsen H, Joslyn G, Stevens J, Spirio L, Robertson M, Sargeant L, Krapcho K, Wolff E, Burt R, Hughes JP, Warrington J, McPherson J, Wasmuth J, Paslier DL, Abderrahim H, Cohen D, Leppert M, White R (1991) Identification and characterization of the familial adenomatous polyposis coli gene. Cell 66:589–600
Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smith AM, Bos JL (1988) Genetic alterations during colorectal tumor development. N Engl J Med 319:525–532
Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61:759–767
Fearon ER, Cho KR, Nigro JM, Kern SE, Simons JW, Ruppert JM, Hamilton SR, Preisinger AC, Thomas G, Kinzler KW, Vogelstein B (1990) Identification of a chromosome 18q gene that is altered in colorectal cancers. Science 247:49–56
Okawa K, Sakamoto M, Hirohashi S, Yoshida Y, Sugimura T, Terada M, Yokota J (1993) Concordant p53 and DCC alterations and allelic losses on chromosomes 13q and 14q associated with liver metastases of colorectal carcinoma. Int J Cancer 53:382–387
Miyaki M, Seki M, Okamoto M, Yamanaka A, Maeda Y, Tanaka K, Kikuchi R, lwama T, lkeuchi T, Tonomura A, Nakamura Y, White R, Miki Y, Utsunomiya J, Koike M (1990) Genetic changes and histopathological types in colorectal tumors from patients with familial adenomatous polyposis, Cancer Res 50:7166–7173
Kikuchi-Yanoshita R, Konishi M, Hukunari H, Tanaka K, Miyaki M (1992) Loss of expression of the DCC gene during progression of colorectal carcinomas in familial adenomatous polyposis and non-familial adenomatous polyposis patients. Cancer Res 52:3801–3803
Hirohashi S, Sugimura T (1991) Genetic alterations in human gastric cancer. Cancer Cells 3:49–52
Tamura G, Kihana T, Nomura K, Terada M, Sugimura T, Hirohashi S (1991) Detection of p53 gene mutations in primary gastric cancer by cell sorting and polymerase chain reaction single-strand conformation polymorphism analysis. Cancer Res 51:3056–3058
Neuman WL, Wasylyshyn ML, Jacoby R, Erroi F, Angriman I, Montag A, Brasitus T, Michelassi F, Westbrook CA (1991) Evidence for common molecular pathogenesis in colorectal, gastric, and pancreatic cancer. Genes, Chromosomes Cancer 3:468–473
Uchino S, Tsuda H, Noguchi M, Yokota J, Terada M, Saito T, Kobayashi M, Sugimura T, Hirohashi S (1992) Frequent loss of hetrozygosity at the DCC locus in gastric cancer. Cancer Res 52:3099–3102
Thompson AM, Morris RG, Wallace M, Wyllie AH, Steel CM, Carter DC (1993) Allele loss from 5q21 (APC/MCC) and 18q21 (DCC) and DCC mRNA expression in breast cancer. Br J Cancer 68:64–68
Shiseki M, Kohno T, Nishikawa R, Sameshima Y, Mizoguchi H, Yokota J (1994) Frequent allelic losses on chromosomes 2q, 18q, and 22q in advanced non-small cell lung carcinoma. Cancer Res 54:5643–5648
Chomczinski P, Sacchi N (1987) Single step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159
Saiki RK, Scharf S, Faloona F, Mullis KB, Horn GT, Erlich HA, Arnheim N (1985) Enzymatic amplyfication of β-gulobin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 230:1350–1354
Veres G, Gibbs RA, Scherer SE, Caskey CT (1987) The molecular basis of the sparse fur mouse mutation. Science 237:415–417
Japanese Research Society for Gastric Cancer (1993) General rules for gastric cancer study, 12th edn (in Japanese). Kanehara, Tokyo
Japanese Research Society for Cancer of Colon and Rectum (1985) General rules for clinical and pathological studies on cancer of colon, rectum and anus, 4th edn (in Japanese). Kanehara, Tokyo
Edelman GM (1988) Morphoregulatory molecules. Biochemistry 27:3533–3543
Tanaka K, Oshimura M, Kikuchi R, Seki M, Hayashi T, Miyaki M (1991) Suppression of tumorigenicity in human colon carcinoma cells by introduction of normal chromosome 5 or 18. Nature 349:340–342
Narayanan R, Lawlor KG, Schaapveld RQJ, Cho KR, Vogelstein B, Tran PB-V, Osborne MP, Telang NT (1992) Antisense RNA to the putative tumor-suppressor gene DCC transforms Rat-1 fibroblasts. Oncogene 7:553–561
Hohne MW, Halatsch ME, Kahl GF, Weinel RJ (1992) Frequent loss of expression of the potential tumor suppressor gene DCC in ductal pancreatic adenocarcinoma. Cancer Res 52:2616–2619
Itoh F, Hinoda Y, Ohe M, Ohe Y, Ban T, Endo T, Imai K, Yachi A (1993) Decreased expression of DCC mRNA in human colorectal cancers. Int J Cancer 53:260–263
Gao X, Honn KV, Grignon D, Sakr W, Chen Q (1993) Frequent loss of expression and loss of heterozygosity of the putative tumor suppressor gene DCC in pancreatic carcinomas. Cancer Res 53:2723–2727
Miyake K, Inokuchi K, Dan K, Nomura T (1993) Alteration in the deleted-in-colorectal-carcinoma gene in human primary leukemia. Blood 82:927–930
Kakeda A, Okabayashi T, Nakatani S, Nakashima A, Johira H, Kataoka M, Orita K (1993) Expression of nm23 mRNA in gastric carcinomas by RT-PCR (in Japanese with English abstract). J Jpn Res Soc Gastroenterol Carcinogenesis 5:61–64
Kataoka M, Okabayashi T, Nakashima A, Nakatani S, Johira H, Takeda A, Orita K (1993) Aberration of p53 gene in gastric and colorectal cancer and the relation with clinicopathological findings (in Japanese with English abstract). J Jpn Res Soc Gastroenterol Carcinogenesis 5:227–230
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Kataoka, M., Okabayashi, T. & Orita, K. Decreased expression of DCC mRNA in gastric and colorectal cancer. Surg Today 25, 1001–1007 (1995). https://doi.org/10.1007/BF00311682
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DOI: https://doi.org/10.1007/BF00311682