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Gut. Dec 1994; 35(12): 1742–1746.
PMCID: PMC1375263

Divergent effects of epidermal growth factor and calcipotriol on human rectal cell proliferation.

Abstract

Vitamin D may protect against colorectal cancer by reducing cell proliferation and inducing differentiation. By contrast, epidermal growth factor (EGF) stimulates cell proliferation and may encourage gastrointestinal mucosal healing. This study investigated the effect of a synthetic vitamin D analogue, calcipotriol, and EGF on human rectal epithelial cell proliferation in patients with familial adenomatous polyposis (FAP). In addition, a new technique to measure the cell cycle time is described. Sigmoidoscopic biopsy specimens were obtained from 14 patients with FAP. Tissue was established in organ culture, with or without the addition of EGF (n = 8), or calcipotriol (n = 6). Proliferation was determined using (a) metaphase arrest to measure the crypt cell production rate, (b) native mitotic index, and (c) the growth fraction using PC10 antibody. EGF receptor expression was shown using a polyclonal antibody AP12E. Calcipotriol reduced crypt cell production rate by 52% from mean (SEM) 5.29 (1.18) to 2.56 (0.80) cells/crypt/hour (p < 0.01) and EGF increased crypt cell production rate by 102% from 3.62 (0.59) to 7.33 (0.90) cells/crypt/hour (p < 0.05), and this tissue expressed the EGF receptor. The growth fraction was 48.40 (4.0)%, and the native mitotic index 1.08 (0.14)%. The cell cycle time was estimated as 94.5 hours and the time for mitosis as one hour. Thus, calcipotriol and EGF have divergent effects on human rectal mucosal proliferation.

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  • Herrera L, Kakati S, Gibas L, Pietrzak E, Sandberg AA. Gardner syndrome in a man with an interstitial deletion of 5q. Am J Med Genet. 1986 Nov;25(3):473–476. [PubMed]
  • Bodmer WF, Bailey CJ, Bodmer J, Bussey HJ, Ellis A, Gorman P, Lucibello FC, Murday VA, Rider SH, Scambler P, et al. Localization of the gene for familial adenomatous polyposis on chromosome 5. Nature. 1987 Aug 13;328(6131):614–616. [PubMed]
  • Leppert M, Dobbs M, Scambler P, O'Connell P, Nakamura Y, Stauffer D, Woodward S, Burt R, Hughes J, Gardner E, et al. The gene for familial polyposis coli maps to the long arm of chromosome 5. Science. 1987 Dec 4;238(4832):1411–1413. [PubMed]
  • Lynch HT, Smyrk T, Lanspa SJ, Marcus JN, Kriegler M, Lynch JF, Appelman HD. Flat adenomas in a colon cancer-prone kindred. J Natl Cancer Inst. 1988 Apr 20;80(4):278–282. [PubMed]
  • Burt RW, Bishop DT, Cannon LA, Dowdle MA, Lee RG, Skolnick MH. Dominant inheritance of adenomatous colonic polyps and colorectal cancer. N Engl J Med. 1985 Jun 13;312(24):1540–1544. [PubMed]
  • Cannon-Albright LA, Skolnick MH, Bishop DT, Lee RG, Burt RW. Common inheritance of susceptibility to colonic adenomatous polyps and associated colorectal cancers. N Engl J Med. 1988 Sep 1;319(9):533–537. [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]
  • Kinzler KW, Nilbert MC, Vogelstein B, Bryan TM, Levy DB, Smith KJ, Preisinger AC, Hamilton SR, Hedge P, Markham A, et al. Identification of a gene located at chromosome 5q21 that is mutated in colorectal cancers. Science. 1991 Mar 15;251(4999):1366–1370. [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]
  • Hill MJ, Morson BC, Bussey HJ. Aetiology of adenoma--carcinoma sequence in large bowel. Lancet. 1978 Feb 4;1(8058):245–247. [PubMed]
  • Boman BM, Levin B. Familial polyposis. Hosp Pract (Off Ed) 1986 May 15;21(5):155–170. [PubMed]
  • Lipkin M, Newmark H. Effect of added dietary calcium on colonic epithelial-cell proliferation in subjects at high risk for familial colonic cancer. N Engl J Med. 1985 Nov 28;313(22):1381–1384. [PubMed]
  • Lipkin M. Biomarkers of increased susceptibility to gastrointestinal cancer: new application to studies of cancer prevention in human subjects. Cancer Res. 1988 Jan 15;48(2):235–245. [PubMed]
  • Terpstra OT, van Blankenstein M, Dees J, Eilers GA. Abnormal pattern of cell proliferation in the entire colonic mucosa of patients with colon adenoma or cancer. Gastroenterology. 1987 Mar;92(3):704–708. [PubMed]
  • Appleton GV, Wheeler EE, Al-Mufti R, Challacombe DN, Williamson RC. Rectal hyperplasia after jejunoileal bypass for morbid obesity. Gut. 1988 Nov;29(11):1544–1548. [PMC free article] [PubMed]
  • Appleton GV, Wheeler EE, Al-Mufti R, Challacombe DN, Williamson RC. Rectal hyperplasia after jejunoileal bypass for morbid obesity. Gut. 1988 Nov;29(11):1544–1548. [PMC free article] [PubMed]
  • Barsoum GH, Hendrickse C, Winslet MC, Youngs D, Donovan IA, Neoptolemos JP, Keighley MR. Reduction of mucosal crypt cell proliferation in patients with colorectal adenomatous polyps by dietary calcium supplementation. Br J Surg. 1992 Jun;79(6):581–583. [PubMed]
  • Thomas MG, Tebbutt S, Williamson RC. Vitamin D and its metabolites inhibit cell proliferation in human rectal mucosa and a colon cancer cell line. Gut. 1992 Dec;33(12):1660–1663. [PMC free article] [PubMed]
  • Thomas MG, Thomson JP, Williamson RC. Oral calcium inhibits rectal epithelial proliferation in familial adenomatous polyposis. Br J Surg. 1993 Apr;80(4):499–501. [PubMed]
  • Binderup L, Bramm E. Effects of a novel vitamin D analogue MC903 on cell proliferation and differentiation in vitro and on calcium metabolism in vivo. Biochem Pharmacol. 1988 Mar 1;37(5):889–895. [PubMed]
  • Kragballe K, Beck HI, Søgaard H. Improvement of psoriasis by a topical vitamin D3 analogue (MC 903) in a double-blind study. Br J Dermatol. 1988 Aug;119(2):223–230. [PubMed]
  • Kragballe K. Treatment of psoriasis by the topical application of the novel cholecalciferol analogue calcipotriol (MC 903) Arch Dermatol. 1989 Dec;125(12):1647–1652. [PubMed]
  • Kragballe K, Gjertsen BT, De Hoop D, Karlsmark T, van de Kerkhof PC, Larkö O, Nieboer C, Roed-Petersen J, Strand A, Tikjøb G. Double-blind, right/left comparison of calcipotriol and betamethasone valerate in treatment of psoriasis vulgaris. Lancet. 1991 Jan 26;337(8735):193–196. [PubMed]
  • Goodlad RA, Wilson TJ, Lenton W, Gregory H, McCullagh KG, Wright NA. Intravenous but not intragastric urogastrone-EGF is trophic to the intestine of parenterally fed rats. Gut. 1987 May;28(5):573–582. [PMC free article] [PubMed]
  • Reeves JR, Richards RC, Cooke T. The effects of intracolonic EGF on mucosal growth and experimental carcinogenesis. Br J Cancer. 1991 Feb;63(2):223–226. [PMC free article] [PubMed]
  • Wright NA, Pike CM, Elia G. Ulceration induces a novel epidermal growth factor-secreting cell lineage in human gastrointestinal mucosa. Digestion. 1990;46 (Suppl 2):125–133. [PubMed]
  • Wright NA, Pike C, Elia G. Induction of a novel epidermal growth factor-secreting cell lineage by mucosal ulceration in human gastrointestinal stem cells. Nature. 1990 Jan 4;343(6253):82–85. [PubMed]
  • Konturek PK, Brzozowski T, Konturek SJ, Dembiński A. Role of epidermal growth factor, prostaglandin, and sulfhydryls in stress-induced gastric lesions. Gastroenterology. 1990 Dec;99(6):1607–1615. [PubMed]
  • Carpenter G. The biochemistry and physiology of the receptor-kinase for epidermal growth factor. Mol Cell Endocrinol. 1983 Jul;31(1):1–19. [PubMed]
  • Bradley SJ, Garfinkle G, Walker E, Salem R, Chen LB, Steele G., Jr Increased expression of the epidermal growth factor receptor on human colon carcinoma cells. Arch Surg. 1986 Nov;121(11):1242–1247. [PubMed]
  • Anzano MA, Rieman D, Prichett W, Bowen-Pope DF, Greig R. Growth factor production by human colon carcinoma cell lines. Cancer Res. 1989 Jun 1;49(11):2898–2904. [PubMed]
  • Huang SA, Lin PF, Fan D, Price JE, Trujillo JM, Chakrabarty S. Growth modulation by epidermal growth factor (EGF) in human colonic carcinoma cells: constitutive expression of the human EGF gene. J Cell Physiol. 1991 Aug;148(2):220–227. [PubMed]
  • Ferguson A, Sutherland A, MacDonald TT, Allan F. Technique for microdissection and measurement in biopsies of human small intestine. J Clin Pathol. 1977 Nov;30(11):1068–1073. [PMC free article] [PubMed]
  • Berger MS, Gullick WJ, Greenfield C, Evans S, Addis BJ, Waterfield MD. Epidermal growth factor receptors in lung tumours. J Pathol. 1987 Aug;152(4):297–307. [PubMed]
  • Sarraf CE, McCormick CS, Brown GR, Price YE, Hall PA, Lane DP, Alison MR. Proliferating cell nuclear antigen immunolocalization in gastro-intestinal epithelia. Digestion. 1991;50(2):85–91. [PubMed]
  • Hall PA, Levison DA, Woods AL, Yu CC, Kellock DB, Watkins JA, Barnes DM, Gillett CE, Camplejohn R, Dover R, et al. Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections: an index of cell proliferation with evidence of deregulated expression in some neoplasms. J Pathol. 1990 Dec;162(4):285–294. [PubMed]
  • Lipkin M, Bell B, Sherlock P. CELL PROLIFERATION KINETICS IN THE GASTROINTESTINAL TRACT OF MAN. I. CELL RENEWAL IN COLON AND RECTUM. J Clin Invest. 1963 Jun;42(6):767–776. [PMC free article] [PubMed]
  • Bleiberg H, Mainguet P, Galand P. Cell renewal in familial polyposis: comparison between polyps and adjacent healthy mucosa. Gastroenterology. 1972 Aug;63(2):240–245. [PubMed]
  • LIPKIN M, SHERLOCK P, BELL BM. Generation time of epithelial cells in the human colon. Nature. 1962 Jul 14;195:175–177. [PubMed]
  • Scott RJ, Hall PA, Haldane JS, van Noorden S, Price Y, Lane DP, Wright NA. A comparison of immunohistochemical markers of cell proliferation with experimentally determined growth fraction. J Pathol. 1991 Oct;165(2):173–178. [PubMed]

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