Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. 1993 Apr 1; 90(7): 2846–2850.

The APC gene product in normal and tumor cells.


The APC gene has been found to be mutated during the development of sporadic colorectal tumors as well as in the germ line of familial adenomatous polyposis patients. To facilitate the characterization of both normal and mutant APC protein, a series of monoclonal and polyclonal antibodies specific for the APC protein was produced. When lymphoblastoid cell lines derived from seven familial adenomatous polyposis patients with known mutations were analyzed by Western blot, an approximately 300-kDa protein corresponding to the predicted size of full-length APC was detected in all 7 cell lines. In addition, truncated APC proteins corresponding to the product of the known mutated alleles could be detected in 4 of the 7 lines. Similar analysis of 23 colon carcinoma and 9 adenoma cell lines revealed truncated proteins in 24 (75%) of the cell lines. Moreover, 26 (81%) of the colon tumor lines were totally devoid of the normal, full-length protein. In contrast, Western blot analysis of 40 cell lines derived from sporadic tumors of other organs detected only full-length APC. Immunohistochemical analysis of APC in normal colonic mucosa revealed cytoplasmic staining with more intense staining in the basolateral margins of the epithelial cell. This staining was markedly increased in the upper portions of the crypts, suggesting an increased level of expression with maturation. These studies provide some initial clues to the function of the cytoplasmic protein APC and demonstrate the feasibility of identifying APC mutations by direct analysis of the APC protein.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.7M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Kinzler KW, Nilbert MC, Su LK, Vogelstein B, Bryan TM, Levy DB, Smith KJ, Preisinger AC, Hedge P, McKechnie D, et al. Identification of FAP locus genes from chromosome 5q21. Science. 1991 Aug 9;253(5020):661–665. [PubMed]
  • 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. [PubMed]
  • Groden J, Thliveris A, Samowitz W, Carlson M, Gelbert L, Albertsen H, Joslyn G, Stevens J, Spirio L, Robertson M, et al. Identification and characterization of the familial adenomatous polyposis coli gene. Cell. 1991 Aug 9;66(3):589–600. [PubMed]
  • Joslyn G, Carlson M, Thliveris A, Albertsen H, Gelbert L, Samowitz W, Groden J, Stevens J, Spirio L, Robertson M, et al. Identification of deletion mutations and three new genes at the familial polyposis locus. Cell. 1991 Aug 9;66(3):601–613. [PubMed]
  • Miyoshi Y, Ando H, Nagase H, Nishisho I, Horii A, Miki Y, Mori T, Utsunomiya J, Baba S, Petersen G, et al. Germ-line mutations of the APC gene in 53 familial adenomatous polyposis patients. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4452–4456. [PMC free article] [PubMed]
  • Miyoshi Y, Nagase H, Ando H, Horii A, Ichii S, Nakatsuru S, Aoki T, Miki Y, Mori T, Nakamura Y. Somatic mutations of the APC gene in colorectal tumors: mutation cluster region in the APC gene. Hum Mol Genet. 1992 Jul;1(4):229–233. [PubMed]
  • Powell SM, Zilz N, Beazer-Barclay Y, Bryan TM, Hamilton SR, Thibodeau SN, Vogelstein B, Kinzler KW. APC mutations occur early during colorectal tumorigenesis. Nature. 1992 Sep 17;359(6392):235–237. [PubMed]
  • Leibovitz A, Stinson JC, McCombs WB, 3rd, McCoy CE, Mazur KC, Mabry ND. Classification of human colorectal adenocarcinoma cell lines. Cancer Res. 1976 Dec;36(12):4562–4569. [PubMed]
  • McBain JA, Weese JL, Meisner LF, Wolberg WH, Willson JK. Establishment and characterization of human colorectal cancer cell lines. Cancer Res. 1984 Dec;44(12 Pt 1):5813–5821. [PubMed]
  • Willson JK, Bittner GN, Oberley TD, Meisner LF, Weese JL. Cell culture of human colon adenomas and carcinomas. Cancer Res. 1987 May 15;47(10):2704–2713. [PubMed]
  • Paraskeva C, Buckle BG, Sheer D, Wigley CB. The isolation and characterization of colorectal epithelial cell lines at different stages in malignant transformation from familial polyposis coli patients. Int J Cancer. 1984 Jul 15;34(1):49–56. [PubMed]
  • Paraskeva C, Finerty S, Mountford RA, Powell SC. Specific cytogenetic abnormalities in two new human colorectal adenoma-derived epithelial cell lines. Cancer Res. 1989 Mar 1;49(5):1282–1286. [PubMed]
  • Williams AC, Harper SJ, Marshall CJ, Gill RW, Mountford RA, Paraskeva C. Specific cytogenetic abnormalities and k-ras mutation in two new human colorectal-adenoma-derived cell lines. Int J Cancer. 1992 Nov 11;52(5):785–790. [PubMed]
  • Koerner TJ, Hill JE, Myers AM, Tzagoloff A. High-expression vectors with multiple cloning sites for construction of trpE fusion genes: pATH vectors. Methods Enzymol. 1991;194:477–490. [PubMed]
  • Baker TA, Grossman AD, Gross CA. A gene regulating the heat shock response in Escherichia coli also affects proteolysis. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6779–6783. [PMC free article] [PubMed]
  • McKenzie SJ, Marks PJ, Lam T, Morgan J, Panicali DL, Trimpe KL, Carney WP. Generation and characterization of monoclonal antibodies specific for the human neu oncogene product, p185. Oncogene. 1989 May;4(5):543–548. [PubMed]
  • Smith DB, Johnson KS. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. Gene. 1988 Jul 15;67(1):31–40. [PubMed]
  • Oliner JD, Kinzler KW, Meltzer PS, George DL, Vogelstein B. Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature. 1992 Jul 2;358(6381):80–83. [PubMed]
  • Sheffield JB, Graff D, Li HP. A solid-phase method for the quantitation of protein in the presence of sodium dodecyl sulfate and other interfering substances. Anal Biochem. 1987 Oct;166(1):49–54. [PubMed]
  • Sprott SC, Hammond KD, Savage N. Subcellular fractionation of murine erythroleukemic cells: distribution of protein kinases. Anal Biochem. 1991 May 1;194(2):407–412. [PubMed]
  • Ashton-Rickardt PG, Wyllie AH, Bird CC, Dunlop MG, Steel CM, Morris RG, Piris J, Romanowski P, Wood R, White R, et al. MCC, a candidate familial polyposis gene in 5q.21, shows frequent allele loss in colorectal and lung cancer. Oncogene. 1991 Oct;6(10):1881–1886. [PubMed]
  • D'Amico D, Carbone DP, Johnson BE, Meltzer SJ, Minna JD. Polymorphic sites within the MCC and APC loci reveal very frequent loss of heterozygosity in human small cell lung cancer. Cancer Res. 1992 Apr 1;52(7):1996–1999. [PubMed]
  • Boynton RF, Blount PL, Yin J, Brown VL, Huang Y, Tong Y, McDaniel T, Newkirk C, Resau JH, Raskind WH, et al. Loss of heterozygosity involving the APC and MCC genetic loci occurs in the majority of human esophageal cancers. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3385–3388. [PMC free article] [PubMed]
  • Hollstein M, Sidransky D, Vogelstein B, Harris CC. p53 mutations in human cancers. Science. 1991 Jul 5;253(5015):49–53. [PubMed]
  • Lim SK, Sigmund CD, Gross KW, Maquat LE. Nonsense codons in human beta-globin mRNA result in the production of mRNA degradation products. Mol Cell Biol. 1992 Mar;12(3):1149–1161. [PMC free article] [PubMed]
  • Dunn JM, Phillips RA, Zhu X, Becker A, Gallie BL. Mutations in the RB1 gene and their effects on transcription. Mol Cell Biol. 1989 Nov;9(11):4596–4604. [PMC free article] [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Cited in Books
    Cited in Books
    NCBI Bookshelf books that cite the current articles.
  • MedGen
    Related information in MedGen
  • OMIM
    Genome Survey Sequence (GSS) nucleotide records reported in the current articles.
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...