Top

Published in:

01-06-2004 | Original Contribution

Effects of Estrogen on Messenger Ribonucleic Acid Expression Patterns of Extracellular Matrix Proteases in the Primate Colon

Authors: Steven Mills, M.D., Kelly A. Young, Ph.D., Mark H. Whiteford, M.D., F.A.C.R.S.

Published in: Diseases of the Colon & Rectum | Issue 6/2004

PURPOSE:

Recent studies suggest that hormone replacement therapy in postmenopausal women can decrease colon cancer risk. To better understand the molecular effects of estrogen on the colon, we examined the effects of estrogen replacement on gene expression of proteases associated with extracellular matrix degradation in rhesus monkey colon tissue.

METHODS:

Rhesus monkeys were oophorectomized and one-half were implanted with estradiol capsules. After five months, colon tissue was harvested, and messenger ribonucleic acid was extracted and converted to cDNA. The cDNA was hybridized with a DNA array spotted with cDNA corresponding to genes involved in extracellular matrix remodeling. Selected genes exhibiting significant differential expression were validated using reverse transcriptase-polymerase chain reaction and real-time polymerase chain reaction analysis.

RESULTS:

Of 96 genes assessed, nearly 18 percent showed a twofold or greater change in expression; however, signals from approximately 65 percent of genes assayed were below detection levels. A distinct pattern of decreased gene expression was observed in colon tissue of animals with estrogen implants compared with females without estrogen replacement. Reverse transcriptase-polymerase chain reaction confirmed decreased expression in estrogen-replaced vs. hormone-deprived tissues of proteases cathepsin-D and caspase-8. Real-time polymerase chain reaction data confirmed the suppression of proteases A disintegrin and mettaloproteinase with thrombospondin motifs, type 1 and matrix metalloproteinase-2 with estrogen replacement in colon tissue.

CONCLUSIONS:

This is the first investigation of the specific effects of estrogen in normal primate colon. Estrogen replacement suppressed expression of several proteases linked to tumor growth and metastasis. This study provides the groundwork for targeted future studies to further characterize the role of estrogen in colon tissue.

Franceschi, S, Gallus, S, Talamini, R, Tavani, A, Negri, E, Vecchia, C 2000Menopause and colorectal cancerBr J Cancer8218602

Kampman, E, Potter, JD, Slattery, ML, Caan, BJ, Edwards, S 1997Hormone replacement therapy, reproductive history, and colon cancer: a multicenter, case-control study in the United StatesCancer Causes Control814658

Rossouw, JE, Anderson, GL, Prentice, RL, et al. 2002Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trialJAMA28832133

Grodstein, F, Newcomb, PA, Stampfer, MJ 1999Postmenopausal hormone therapy and the risk of colorectal cancer: a review and meta-analysisAm J Med10657482

Mahavni, V, Sood, AK 2001Hormone replacement therapy and cancer riskCurr Opin Oncol133849

Troisi, R, Schairer, C, Chow, WH, Schatzkin, A, Brinton, LA, Fraumeni, JF,Jr 1997A prospective study of menopausal hormones and risk of colorectal cancer (United States)Cancer Causes Control81308

Smirnoff, P, Liel, Y, Gnainsky, J, Shany, S, Schwartz, B 1999The protective effect of estrogen against chemically induced murine colon carcinogenesis is associated with decreased CpG island methylation and increased mRNA and protein expression of the colonic vitamin D receptorOncol Res1125564

Qiu, Y, Waters, CE, Lewis, AE, Langman, MJ, Eggo, MC 2002Oestrogen-induced apoptosis in colonocytes expressing oestrogen receptor betaJ Endocrinol17436977

Domenico, M, Castoria, G, Bilancio, A, Migliaccio, A, Auricchio, F 1996Estradiol activation of human colon carcinoma-derived Caco-2 cell growthCancer Res56451621

10.

Singh, S, Paraskeva, C, Gallimore, PH, Sheppard, MC, Langman, MJ 1994Differential growth response to oestrogen of premalignant and malignant colonic cell linesAnticancer Res14103741

11.

Harvey, BJ, Doolan, CM, Condliffe, SB, Renard, C, Alzamora, R, Urbach, V 2002Non-genomic convergent and divergent signalling of rapid responses to aldosterone and estradiol in mammalian colonSteroids6748391

12.

Singh, S, Poulsom, R, Hanby, AM, et al. 1998Expression of oestrogen receptor and oestrogen-inducible genes pS2 and ERD5 in large bowel mucosa and cancerJ Pathol18415360

13.

Carothers, AM, Hughes, SA, Ortega, D, Bertagnolli, MM 20022-Methoxyestradiol induces p53-associated apoptosis of colorectal cancer cellsCancer Lett1877786

14.

Nakayama, Y, Sakamoto, H, Satoh, K, Yamamoto, T 2000Tamoxifen and gonadal steroids inhibit colon cancer growth in association with inhibition of thymidylate synthase, survivin and telomerase expression through estrogen receptor beta mediated systemCancer Lett1616371

15.

Rochefort, H, Chalbos, D, Cunat, S, Lucas, A, Platet, N, Garcia, M 2001Estrogen regulated proteases and antiproteases in ovarian and breast cancer cellsJ Steroid Biochem Mol Bio7611924

16.

Kuno, K, Kanada, N, Nakashima, E, Fujiki, F, Ichimura, F, Matsushima, K 1997Molecular cloning of a gene encoding a new type of metalloproteinase-disintegrin family protein with thrombospondin motifs as an inflammation associated geneJ Biol Chem27255662

17.

LaVallee, TM, Zhan, XH, Johnson, MS, et al. 20032-methoxyestradiol up-regulates death receptor 5 and induces apoptosis through activation of the extrinsic pathwayCancer Res6346875

18.

Papadopoulou, S, Scorilas, A, Arnogianaki, N, et al. 2001Expression of gelatinase-A (MMP-2) in human colon cancer and normal colon mucosaTumour Biol223839

19.

Sardinha, TC, Nogueras, JJ, Xiong, H, Weiss, EG, Wexner, SD, Abramson, S 2000Membrane-type 1 matrix metalloproteinase mRNA expression in colorectal cancerDis Colon Rectum4338995

20.

Molskness, TA, Woodruff, TK, Hess, DL, Dahl, KD, Stouffer, RL 1996Recombinant human inhibin-A administered early in the menstrual cycle alters concurrent pituitary and follicular, plus subsequent luteal, function in rhesus monkeysJ Clin Endocrinol Metab8140026

21.

Otto, LN, Slayden, OD, Clark, AL, Brenner, RM 2002The rhesus macaque as an animal model for pelvic organ prolapseAm J Obstet Gynecol18641621

22.

Slayden, OD, Hirst, JJ, Brenner, RM 1993Estrogen action in the reproductive tract of rhesus monkeys during antiprogestin treatmentEndocrinology132184556

23.

Chaffin, CL, Stouffer, RL 1999Expression of matrix metalloproteinases and their tissue inhibitor messenger ribonucleic acids in macaque periovulatory granulosa cells: time course and steroid regulationBiol Reprod611421

24.

Young, KA, Hennebold, JD, Stouffer, RL 2002Dynamic expression of mRNAs and proteins for matrix metalloproteinases and their tissue inhibitors in the primate corpus luteum during the menstrual cycleMol Hum Reprod883340

25.

Diaz, GD, Li, Q, Dashwood, RH 2003Caspase-8 and apoptosis-inducing factor mediate a cytochrome c-independent pathway of apoptosis in human colon cancer cells induced by the dietary phytochemical chlorophyllinCancer Res63125461

26.

Malhotra, S, Newman, E, Eisenberg, D, et al. 2002Increased membrane type 1 matrix metalloproteinase expression from adenoma to colon cancer: a possible mechanism of neoplastic progressionDis Colon Rectum4553743

27.

Smits, P, Ni, J, Feng, P, et al. 1997The human extracellular matrix gene 1 (ECM1): genomic structure, cDNA cloning, expression pattern, and chromosomal localizationGenomics4548795

28.

Theodoropoulos, GE, Panoussopoulos, D, Lazaris, AC, Golematis, BC 1997Evaluation of cathepsin D immunostaining in colorectal adenocarcinomaJ Surg Oncol652428

29.

Ornstein, DL, Cohn, KH 2002Balance between activation and inhibition of matrix metalloproteinase-2 (MMP-2) is altered in colorectal tumors compared to normal colonic epitheliumDig Dis Sci47182130

30.

Jemal, A, Murray, T, Samuels, A, Ghafoor, A, Ward, E, Thun, MJ 2003Cancer statistics, 2003CA Cancer J Clin53526

31.

Hartman, C, Straus, W 1961The anatomy of the rhesus monkey (Macaca mulatta)Hafner Publishing CoNew York21923

32.

Johnson, EH, Morgenstern, SE, Perham, JM, Barthold, SW 1996Colonic adenocarcinoma in a rhesus macaque (Macaca mulatta)J Med Primatol254358

33.

Lembo, TM, Tinkey, PT, Cromeens, DM, Gray, KN, Price, RE 1997Stenosing colonic adenocarcinoma in a female rhesus monkeyJ Med Primatol2622932

34.

O’Sullivan, MG, Carlson, CS 2001Colonic adenocarcinoma in rhesus macaquesJ Comp Pathol1242125

35.

Uno, H, Alsum, P, Zimbric, ML, Houser, WD, Thomson, JA, Kemnitz, JW 1998Colon cancer in aged captive rhesus monkeys (Macaca mulatta)Am J Primatol441927

36.

Stetler-Stevenson, WG, Aznavoorian, S, Liotta, LA 1993Tumor cell interactions with the extracellular matrix during invasion and metastasisAnnu Rev Cell Biol954173

37.

Foekens, JA, Look, MP, Bolt-de Vries, J, Meijer-van Gelder, ME, Putten, WL, Klijn, JG 1999Cathepsin-D in primary breast cancer: prognostic evaluation involving 2810 patientsBr J Cancer793007

38.

Westley, B, Rochefort, H 1980A secreted glycoprotein induced by estrogen in human breast cancer cell linesCell2035362

39.

Cohen, GM 1997Caspases: the executioners of apoptosisBiochem J326116

40.

Rupa, JD, Bruine, AP, Gerbers, AJ, et al. 2003Simultaneous detection of apoptosis and proliferation in colorectal carcinoma by multiparameter flow cytometry allows separation of high and low-turnover tumors with distinct clinical outcomeCancer97240411

41.

Vakkala, M, Paakko, P, Soini, Y 1999Expression of caspases 3, 6 and 8 is increased in parallel with apoptosis and histological aggressiveness of the breast lesionBr J Cancer815929

42.

Zhang, Y, Tounekti, O, Akerman, B, Goodyer, CG, LeBlanc, A 200117-beta-estradiol induces an inhibitor of active caspasesJ Neurosci21RC176

43.

Okada, A, Bellocq, JP, Rouyer, N, et al. 1995Membrane-type matrix metalloproteinase (MT-MMP) gene is expressed in stromal cells of human colon, breast, and head and neck carcinomasProc Natl Acad Sci9227304

44.

Robker, RL, Russell, DL, Espey, LL, Lydon, JP, O’Malley, BW, Richards, JS 2000Progesterone-regulated genes in the ovulation process: ADAMTS-1 and cathepsin L proteasesProc Natl Acad Sci U S A97468994

45.

Moalli, PA, Klingensmith, WL, Meyn, LA, Zyczynski, HM 2002Regulation of matrix metalloproteinase expression by estrogen in fibroblasts that are derived from the pelvic floorAm J Obstet Gynecol187729

46.

Zhang, P, Zhong, M 2001Effects of 17beta-estradiol and progesterone on the expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in rat osteoblastsDi Yi Jun Yi Da Xue Xue Bao2192931

47.

Puistola, U, Westerlund, A, Kauppila, A, Turpeenniemi-Hujanen, T 1995Regulation of 72-kd type IV collagenase-matrix metalloproteinase-2 by estradiol and gonadotropin-releasing hormone agonist in human granulosa-lutein cellsFertil Steril64817

48.

Nelson, RL, Dollear, T, Freels, S, Persky, V 1997The relation of age, race, and gender to the subsite location of colorectal carcinomaCancer801937

49.

McCashland, TM, Brand, R, Lyden, E, Garmo, P 2001CORI Research Project. Gender differences in colorectal polyps and tumorsAm J Gastroenterol968826

Title: Effects of Estrogen on Messenger Ribonucleic Acid Expression Patterns of Extracellular Matrix Proteases in the Primate Colon
Authors: Steven Mills, M.D.
Kelly A. Young, Ph.D.
Mark H. Whiteford, M.D., F.A.C.R.S.
Publication date: 01-06-2004
Publisher: Springer-Verlag
Published in: Diseases of the Colon & Rectum / Issue 6/2004
Print ISSN: 0012-3706
Electronic ISSN: 1530-0358
DOI: https://doi.org/10.1007/s10350-004-0510-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Effects of Estrogen on Messenger Ribonucleic Acid Expression Patterns of Extracellular Matrix Proteases in the Primate Colon

PURPOSE:

METHODS:

RESULTS:

CONCLUSIONS:

Keynote webinar | Spotlight on medication adherence

Springer Medicine

PURPOSE:

METHODS:

RESULTS:

CONCLUSIONS:

Please log in to get access to this content

Other articles of this Issue 6/2004

XXth Biennial Congress of the ISUCRS

Dis Colon Rectum, Vol. 47, No. 3, March 2004, pp. 271–278

Open vs. Closed Lateral Internal Sphincterotomy for Idiopathic Fissure-in-Ano: A Prospective, Randomized, Controlled Trial

Practice Parameters for the Surveillance and Follow-Up of Patients With Colon and Rectal Cancer

Is Pouchitis a Clinical, Endoscopic, or Histologic Problem?

Neoadjuvant Therapy for Rectal Cancer: Histologic Response of the Primary Tumor Predicts Nodal Status