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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 May 1;90(9):4166–4170. doi: 10.1073/pnas.90.9.4166

Identification of a colon mucosa gene that is down-regulated in colon adenomas and adenocarcinomas.

C W Schweinfest 1, K W Henderson 1, S Suster 1, N Kondoh 1, T S Papas 1
PMCID: PMC46467  PMID: 7683425

Abstract

A cDNA, which we call DRA (for down-regulated in adenoma) has been isolated. Its mRNA is expressed exclusively in normal colon tissue, probably only in the mucosal epithelia. Expression of the DRA gene is significantly decreased in adenomas (polyps) and adenocarcinomas of the colon. The DRA gene appears to be a single-copy gene present on chromosome 7, a chromosome associated with colorectal tumorigenesis. The predicted DRA polypeptide is an 84,500-Da protein that contains charged clusters of amino acids, primarily at the NH2 and COOH termini. Together with potential nuclear targeting motifs, an acidic transcriptional activation domain, and a homeobox domain, these elements suggest a transcription factor or a protein that may interact with transcription factors. Such a function may be consistent with a role in tissue-specific gene expression and/or as a candidate tumor-suppressor gene.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Augenlicht L. H., Taylor J., Anderson L., Lipkin M. Patterns of gene expression that characterize the colonic mucosa in patients at genetic risk for colonic cancer. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3286–3289. doi: 10.1073/pnas.88.8.3286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baker S. J., Fearon E. R., Nigro J. M., Hamilton S. R., Preisinger A. C., Jessup J. M., vanTuinen P., Ledbetter D. H., Barker D. F., Nakamura Y. Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science. 1989 Apr 14;244(4901):217–221. doi: 10.1126/science.2649981. [DOI] [PubMed] [Google Scholar]
  3. Baker S. J., Markowitz S., Fearon E. R., Willson J. K., Vogelstein B. Suppression of human colorectal carcinoma cell growth by wild-type p53. Science. 1990 Aug 24;249(4971):912–915. doi: 10.1126/science.2144057. [DOI] [PubMed] [Google Scholar]
  4. Bos J. L., Fearon E. R., Hamilton S. R., Verlaan-de Vries M., van Boom J. H., van der Eb A. J., Vogelstein B. Prevalence of ras gene mutations in human colorectal cancers. 1987 May 28-Jun 3Nature. 327(6120):293–297. doi: 10.1038/327293a0. [DOI] [PubMed] [Google Scholar]
  5. Brendel V., Karlin S. Association of charge clusters with functional domains of cellular transcription factors. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5698–5702. doi: 10.1073/pnas.86.15.5698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Briggs M. R., Kadonaga J. T., Bell S. P., Tjian R. Purification and biochemical characterization of the promoter-specific transcription factor, Sp1. Science. 1986 Oct 3;234(4772):47–52. doi: 10.1126/science.3529394. [DOI] [PubMed] [Google Scholar]
  7. Burmer G. C., Loeb L. A. Mutations in the KRAS2 oncogene during progressive stages of human colon carcinoma. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2403–2407. doi: 10.1073/pnas.86.7.2403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  9. Cress W. D., Triezenberg S. J. Critical structural elements of the VP16 transcriptional activation domain. Science. 1991 Jan 4;251(4989):87–90. doi: 10.1126/science.1846049. [DOI] [PubMed] [Google Scholar]
  10. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Erisman M. D., Rothberg P. G., Diehl R. E., Morse C. C., Spandorfer J. M., Astrin S. M. Deregulation of c-myc gene expression in human colon carcinoma is not accompanied by amplification or rearrangement of the gene. Mol Cell Biol. 1985 Aug;5(8):1969–1976. doi: 10.1128/mcb.5.8.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fearon E. R., Cho K. R., Nigro J. M., Kern S. E., Simons J. W., Ruppert J. M., Hamilton S. R., Preisinger A. C., Thomas G., Kinzler K. W. Identification of a chromosome 18q gene that is altered in colorectal cancers. Science. 1990 Jan 5;247(4938):49–56. doi: 10.1126/science.2294591. [DOI] [PubMed] [Google Scholar]
  13. Fearon E. R., Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990 Jun 1;61(5):759–767. doi: 10.1016/0092-8674(90)90186-i. [DOI] [PubMed] [Google Scholar]
  14. Feinberg A. P., Gehrke C. W., Kuo K. C., Ehrlich M. Reduced genomic 5-methylcytosine content in human colonic neoplasia. Cancer Res. 1988 Mar 1;48(5):1159–1161. [PubMed] [Google Scholar]
  15. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  16. Finley G. G., Schulz N. T., Hill S. A., Geiser J. R., Pipas J. M., Meisler A. I. Expression of the myc gene family in different stages of human colorectal cancer. Oncogene. 1989 Aug;4(8):963–971. [PubMed] [Google Scholar]
  17. Forrester K., Almoguera C., Han K., Grizzle W. E., Perucho M. Detection of high incidence of K-ras oncogenes during human colon tumorigenesis. 1987 May 28-Jun 3Nature. 327(6120):298–303. doi: 10.1038/327298a0. [DOI] [PubMed] [Google Scholar]
  18. Goelz S. E., Vogelstein B., Hamilton S. R., Feinberg A. P. Hypomethylation of DNA from benign and malignant human colon neoplasms. Science. 1985 Apr 12;228(4696):187–190. doi: 10.1126/science.2579435. [DOI] [PubMed] [Google Scholar]
  19. Goyette M. C., Cho K., Fasching C. L., Levy D. B., Kinzler K. W., Paraskeva C., Vogelstein B., Stanbridge E. J. Progression of colorectal cancer is associated with multiple tumor suppressor gene defects but inhibition of tumorigenicity is accomplished by correction of any single defect via chromosome transfer. Mol Cell Biol. 1992 Mar;12(3):1387–1395. doi: 10.1128/mcb.12.3.1387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Groden J., Thliveris A., Samowitz W., Carlson M., Gelbert L., Albertsen H., Joslyn G., Stevens J., Spirio L., Robertson M. Identification and characterization of the familial adenomatous polyposis coli gene. Cell. 1991 Aug 9;66(3):589–600. doi: 10.1016/0092-8674(81)90021-0. [DOI] [PubMed] [Google Scholar]
  21. Gómez-Márquez J., Segade F. Prothymosin alpha is a nuclear protein. FEBS Lett. 1988 Jan 4;226(2):217–219. doi: 10.1016/0014-5793(88)81425-x. [DOI] [PubMed] [Google Scholar]
  22. Imaseki H., Hayashi H., Taira M., Ito Y., Tabata Y., Onoda S., Isono K., Tatibana M. Expression of c-myc oncogene in colorectal polyps as a biological marker for monitoring malignant potential. Cancer. 1989 Aug 1;64(3):704–709. doi: 10.1002/1097-0142(19890801)64:3<704::aid-cncr2820640323>3.0.co;2-s. [DOI] [PubMed] [Google Scholar]
  23. Kinzler K. W., Nilbert M. C., Su L. K., Vogelstein B., Bryan T. M., Levy D. B., Smith K. J., Preisinger A. C., Hedge P., McKechnie D. Identification of FAP locus genes from chromosome 5q21. Science. 1991 Aug 9;253(5020):661–665. doi: 10.1126/science.1651562. [DOI] [PubMed] [Google Scholar]
  24. Kinzler K. W., Nilbert M. C., Vogelstein B., Bryan T. M., Levy D. B., Smith K. J., Preisinger A. C., Hamilton S. R., Hedge P., Markham A. Identification of a gene located at chromosome 5q21 that is mutated in colorectal cancers. Science. 1991 Mar 15;251(4999):1366–1370. doi: 10.1126/science.1848370. [DOI] [PubMed] [Google Scholar]
  25. Kozak M. An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res. 1987 Oct 26;15(20):8125–8148. doi: 10.1093/nar/15.20.8125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kozak M. An analysis of vertebrate mRNA sequences: intimations of translational control. J Cell Biol. 1991 Nov;115(4):887–903. doi: 10.1083/jcb.115.4.887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kozak M. Context effects and inefficient initiation at non-AUG codons in eucaryotic cell-free translation systems. Mol Cell Biol. 1989 Nov;9(11):5073–5080. doi: 10.1128/mcb.9.11.5073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Lee W., Mitchell P., Tjian R. Purified transcription factor AP-1 interacts with TPA-inducible enhancer elements. Cell. 1987 Jun 19;49(6):741–752. doi: 10.1016/0092-8674(87)90612-x. [DOI] [PubMed] [Google Scholar]
  29. Lehrach H., Diamond D., Wozney J. M., Boedtker H. RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination. Biochemistry. 1977 Oct 18;16(21):4743–4751. doi: 10.1021/bi00640a033. [DOI] [PubMed] [Google Scholar]
  30. Nigro J. M., Baker S. J., Preisinger A. C., Jessup J. M., Hostetter R., Cleary K., Bigner S. H., Davidson N., Baylin S., Devilee P. Mutations in the p53 gene occur in diverse human tumour types. Nature. 1989 Dec 7;342(6250):705–708. doi: 10.1038/342705a0. [DOI] [PubMed] [Google Scholar]
  31. Nishisho I., Nakamura Y., Miyoshi Y., Miki Y., Ando H., Horii A., Koyama K., Utsunomiya J., Baba S., Hedge P. Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science. 1991 Aug 9;253(5020):665–669. doi: 10.1126/science.1651563. [DOI] [PubMed] [Google Scholar]
  32. Paraskeva C., Corfield A. P., Harper S., Hague A., Audcent K., Williams A. C. Colorectal carcinogenesis: sequential steps in the in vitro immortalization and transformation of human colonic epithelial cells (review). Anticancer Res. 1990 Sep-Oct;10(5A):1189–1200. [PubMed] [Google Scholar]
  33. Rau D., Köster A., Tittelbach H., Sachse R., Landgraf S., Neubauer S., Giedl J., Dingermann T., Gebhart E. Chromosome and oncogene studies in human rectal and colon carcinomas. Anticancer Res. 1991 Jul-Aug;11(4):1477–1484. [PubMed] [Google Scholar]
  34. Rodriguez-Alfageme C., Stanbridge E. J., Astrin S. M. Suppression of deregulated c-MYC expression in human colon carcinoma cells by chromosome 5 transfer. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1482–1486. doi: 10.1073/pnas.89.4.1482. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Schweinfest C. W., Henderson K. W., Gu J. R., Kottaridis S. D., Besbeas S., Panotopoulou E., Papas T. S. Subtraction hybridization cDNA libraries from colon carcinoma and hepatic cancer. Genet Anal Tech Appl. 1990 May;7(3):64–70. doi: 10.1016/0735-0651(90)90042-e. [DOI] [PubMed] [Google Scholar]
  36. Willson J. K., Bittner G. N., Oberley T. D., Meisner L. F., Weese J. L. Cell culture of human colon adenomas and carcinomas. Cancer Res. 1987 May 15;47(10):2704–2713. [PubMed] [Google Scholar]
  37. el-Deiry W. S., Nelkin B. D., Celano P., Yen R. W., Falco J. P., Hamilton S. R., Baylin S. B. High expression of the DNA methyltransferase gene characterizes human neoplastic cells and progression stages of colon cancer. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3470–3474. doi: 10.1073/pnas.88.8.3470. [DOI] [PMC free article] [PubMed] [Google Scholar]

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