nach oben

Breast Cancer Research and Treatment

Erschienen in:

01.06.2008 | Preclinical Study

Precancerous model of human breast epithelial cells induced by NNK for prevention

verfasst von: Nalin Siriwardhana, Shambhunath Choudhary, Hwa-Chain Robert Wang

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 3/2008

Einloggen, um Zugang zu erhalten

Abstract

Epidemiological investigations have suggested that exposure to tobacco and environmental carcinogens increase the risk of developing human breast cancer. In light of the chronic exposure of human breast tissues to tobacco and environmental carcinogens, we have taken an approach of analyzing cellular changes of immortalized non-cancerous human breast epithelial MCF10A cells during the acquisition of cancerous properties induced by repeated exposure to the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) at a low concentration of 100 pM. We found that accumulated exposures of MCF10A cells to NNK result in progressive development of cellular carcinogenesis from a stage of immortalization to precancerous sub-stages of acquiring a reduced dependence on growth factors and acquiring anchorage-independent growth. Using Matrigel for MCF10A cells to form size-restricted acini, we detected that exposures to NNK resulted in altered acinar conformation. Analysis of gene expression profiles by cDNA microarrays revealed up- and down-regulated genes associated with NNK-induced carcinogenesis. Using this cellular carcinogenesis model as a target system to identify anticancer agents, we detected that grape seed proanthocyanadin extract significantly suppressed NNK-induced carcinogenesis of MCF10A cells. Our studies provide a carcinogenesis-cellular model mimicking the accumulative exposure to carcinogens in the progression of human breast epithelial cells to increasingly acquire cancerous properties, as likely occurs in the development of precancerous human breast cells. Our cellular model also serves as a cost-efficient, in vitro system to identify preventive agents that inhibit human breast cell carcinogenesis induced by chronic exposures to carcinogens.

Guengerich FP (2000) Metabolism of chemical carcinogens. Carcinogenesis 21:345–351PubMedCrossRef

Kelloff GJ, Hawk ET, Sigman CC (eds) (2005) Cancer chemoprevention. Human Press, NJ

Lichtenstein P, Holm NV, Verkasalo PK et al (2000) Environmental and heritable factors in the causation of cancer analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 343:78–85PubMedCrossRef

Grover PL, Martin FL (2002) The initiation of breast and prostate cancer. Carcinogenesis 23:1095–1102PubMedCrossRef

DeBruin LS, Josephy PD (2002) Perspectives on the chemical etiology of breast cancer. Environ Health Perspect 110(Suppl. 1):119–128PubMed

Hecht SS (2002) Tobacco smoke carcinogens and breast cancer. Environ Mol Mutagen 39:119–126PubMedCrossRef

Gorlewska RK, Green B, Fares M et al (2002) Carcinogen-DNA adducts in human breast epithelial cells. Environ Mol Mutagen 39:184–192CrossRef

Wogan GN, Hecht SS, Felton JS et al (2004) Environmental and chemical carcinogenesis. Seminars Cancer Biol 14:473–486CrossRef

Reynolds P, Hurley S, Goldberg DE et al (2004) Active smoking, household passive smoking, and breast cancer: evidence from the California Teachers Study. J Natl Cancer Inst 96:29–37PubMedCrossRef

10.

Li D, Zhang W, Sahin AA, Hittelman WN (1999) DNA adducts in normal tissue adjacent to breast cancer: a review. Cancer Detect Prev 23:454–462PubMedCrossRef

11.

Barrett JC, Shelby MD (1992) Mechanisms of human carcinogens. Prog Clin Biol Res 374:415–434PubMed

12.

Miller EC, Miller JA (1981) Mechanisms of chemical carcinogenesis. Cancer 147:1055–1064CrossRef

13.

O’Shaughnessy JA, Kelloff GJ, Gordon GB et al (2002) Treatment and prevention of intraepithelial neoplasia: an important target for accelerated new agent development. Clin Cancer Res 8:314–346PubMed

14.

Sanders ME, Schuyler PA, Dupont WD, Page DL (2005) The natural history of low-grade ductal carcinoma in situ of the breast in women treated by biopsy only revealed over 30 years of long-term follow-up. Cancer 103:2481–2484PubMedCrossRef

15.

Hecht SS, Hatsukami DK, Bonilla LE, Hochalter JB (1999) Quantitation of 4-oxo-4-(3-pyridyl)butanoic acid and enantiomers of 4-hydroxy-4-(3-pyridyl)butanoic acid in human urine: a substantial pathway of nicotine metabolism. Chem Res Toxicol 12:172–179PubMedCrossRef

16.

Hecht SS, Carmella SG, Chen M et al (1999) Quantitation of urinary metabolites of a tobacco-specific lung carcinogen after smoking cessation. Cancer Res 59:590–596PubMed

17.

Besaratinia A, Maas LM, Brouwer EM et al (2002) A molecular dosimetry approach to assess human exposure to environmental tobacco smoke in pubs. Carcinogenesis 23:1171–1176PubMedCrossRef

18.

Hecht SS (1996) Recent studies on mechanisms of bioactivation and detoxification of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco specific lung carcinogen. Crit Rev Toxicol 26:163–181PubMedCrossRef

19.

Hecht SS (1999) Tobacco smoke carcinogens and lung cancer. J Natl Cancer Inst 91:1194–1210PubMedCrossRef

20.

Wu Z, Upadhyaya P, Carmella SG et al (2002) Disposition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in bile duct-cannulated rats: Steroselective metabolism and tissue distribution. Carcinogenesis 23:171–179PubMedCrossRef

21.

Chhabra SK, Anderson LM, Perella C et al (2000) Coexposure to ethanol with N-nitrosodimethylamine or 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone during lactation of rats: marked increase in O(6)-methylguanine-DNA adducts in maternal mammary gland and in suckling lung and kidney. Toxicol Appl Pharmacol 169:191–200PubMedCrossRef

22.

Mei J, Hu H, McEntee M et al (2003) Transformation of noncancerous human breast epithelial cell MCF10A induced by the tobacco-specific carcinogen NNK. Breast Cancer Res Treat 79:95–105PubMedCrossRef

23.

Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70PubMedCrossRef

24.

Schwab M (2001) Oncogene. In: Schwab M (ed) Encyclopedic reference of cancer. Springer-Verlag, New York, pp 649–652

25.

Soule HD, Maloney TM, Wolman SR et al (1990) Isolation and characterization of a spontaneously immortalized human breast epithelial cell line, MCF-10. Cancer Res 50:6075–6086PubMed

26.

Debnath J, Muthuswamy SK, Brugge JS (2003) Morphogenesis and oncogenesis of MCF-10A mammary epithelial acini grown in three-dimensional basement membrane cultures. Methods 30:256–268PubMedCrossRef

27.

Specht K, Kremer M, Müller U et al (2002) Quintanilla-Martinez L, and Fend F. Identification of Cyclin D1 mRNA Overexpression in B-Cell Neoplasias by Real-Time Reverse Transcription-PCR of Microdissected Paraffin Sections. Clin Cancer Res 8:2902–2911PubMed

28.

Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT Method. Methods 23:402–408CrossRef

29.

Yuan JS, Reed A, Chen F, Stewart CN (2006) Statistical analysis of real-time PCR data. BMC Bioinformatics 7:85PubMedCrossRef

30.

Fecteau KA, Mei J, Wang HCR (2002) Differential modulation of signaling pathways and apoptosis of ras-transformed 10T1/2 cells by the depsipeptide FR901228. J Pharmacol Exp Ther 300:890–899PubMedCrossRef

31.

Debnath J, Brugge JS (2005) Modelling glandular epithelial cancers in three-dimensional cultures. Nat Rev Cancer 5:675–688PubMedCrossRef

32.

Nelson CM, Bissell MJ (2005) Modeling dynamic reciprocity: engineering three-dimensional culture models of breast architecture, function, and neoplastic transformation. Semin Cancer Biol 15:342–352PubMedCrossRef

33.

Ye X, Krohn RL, Liu W et al (1999) The cytotoxic effects of a novel IH636 grape seed proanthocyanidin extract on cultured human cancer cells. Mol Cell Biochem 196:99–108PubMedCrossRef

34.

Bagchi D, Bagchi M, Stohs S et al (2002) Cellular protection with proanthocyanidins derived from grape seeds. Ann NY Acad Sci 957:260–270PubMedCrossRef

35.

Sharma G, Tyagi AK, Singh RP et al (2004) Synergistic anti-cancer effects of grape seed extract and conventional cytotoxic agent doxorubicin against human breast carcinoma cells. Breast Cancer Res Treat 85:1–12PubMedCrossRef

36.

Kim H, Hall P, Smith M et al (2004) Chemoprevention by grape seed extract and genistein in carcinogen-induced mammary cancer in rats is diet dependent. J Nutr 134:3445S–3452SPubMed

37.

Cos P, De Bruyne T, Hermans N et al (2004) Proanthocyanidins in health care: current and new trends. Curr Med Chem 11:1345–1359PubMed

38.

Ray SD, Bagchi D (2005) Roles of polyphenols, flavonoids, and oligomeric preoanthocyanidins. In: Bagchi D, Preuss HG (eds) Cancer chemoprevention. CRC Press, FL

39.

Faria A, Calhau C, de Freitas V, Mateus N (2006) Procyanidins as antioxidants and tumor cell growth modulators. J Agric Food Chem 54:2392–2397PubMedCrossRef

40.

Safe S, Abdelrahim M (2005) Sp transcription factor family and its role in cancer. Eur J Cancer 41:2438–2448PubMedCrossRef

41.

Abdelrahim M, Baker CH, Abbruzzese JL, Safe S (2006) Tolfenamic acid and pancreatic cancer growth, angiogenesis, and Sp protein degradation. J Natl Cancer Inst 98:855–868PubMedCrossRef

42.

Chelouche-Lev D, Kluger HM, Berger AJ et al (2004) αB-crystallin as a marker of lymph node involvement in breast carcinoma. Cancer 100:2543–2548PubMedCrossRef

43.

Moyano JV, Evans JR, Chen F et al (2006) αB-Crystallin is a novel oncoprotein that predicts poor clinical outcome in breast cancer. J Clin Invest 116:261–270PubMedCrossRef

44.

Sasano H, Frost AR, Saitoh R et al (1997) Localization of mineralocorticoid receptor and 11 beta-hydroxysteroid dehydrogenase type II in human breast and its disorders. Anticancer Res 17(3C):2001–2007PubMed

45.

Moggs JG, Murphy TC, Lim FL et al (2005) Anti-proliferative effect of estrogen in breast cancer cells that re-express ERα is mediated by aberrant regulation of cell cycle genes. J Mol Endocrinol 34:535–551PubMedCrossRef

46.

Bertucci F, Finetti P, Rougemont J (2005) Gene expression profiling identifies molecular subtypes of inflammatory breast cancer. Cancer Res 65:2170–2178PubMedCrossRef

47.

Walss-Bass C, Xu K, David S et al (2002) Occurrence of nuclear beta II-tubulin in cultured cells. Cell Tissue Res 308:215–223PubMedCrossRef

48.

Liu D, Rudland PS, Sibson DR et al (2000) Expression of calcium-binding protein S100A2 in breast lesions. Br J Cancer 83:1473–1479PubMedCrossRef

49.

Cheng M, Watson PH, Paterson JA et al (1997) Pro-protein convertase gene expression in human breast cancer. Int J Cancer 71:966–971PubMedCrossRef

50.

Pedersen N, Mortensen S, Sorensen SB et al (2003) Transcriptional gene expression profiling of small cell lung cancer cells. Cancer Res 63:1943–1953PubMed

51.

Iwai K, Hirata K, Ishida T et al (2004) An anti-proliferative gene BTG1 regulates angiogenesis in vitro. Biochem Biophys Res Comm 316:628–635PubMedCrossRef

52.

Van der Heijden MC, Verhagen JN, Rijksen G et al (1986) Phosphofructokinase in normal thyroid tissue and thyroid neoplasms. Tumor Biol 7:9–18

53.

Wilkinson S, Paterson HF, Marshall CJ (2005) Cdc42-MRCK and Rho-ROCK signalling cooperate in myosin phosphorylation and cell invasion. Nat Cell Biol 7:255–261PubMedCrossRef

54.

Murakami M, Nakashima K, Kamei D et al (2003) Cellular prostaglandin E₂ production by membrane-bound prostaglandin E synthase-2 via both cyclooxygenase-1 and -2. J Biol Chem 278:37937–37947PubMedCrossRef

55.

Yoshida K, Miki Y (2004) Role of BRCA1 and BRCA2 as regulators of DNA repair, transcription, and cell cycle in response to DNA damage. Cancer Sci 95:866–871PubMedCrossRef

56.

Abaji C, Cousineau I, Belmaaza A et al (2005) BRCA2 regulates homologous recombination in response to DNA damage: implications for genome stability and carcinogenesis. Cancer Res 65:4117–4125PubMedCrossRef

57.

Russo J, Calaf G, Russo IH (1993) A critical approach to the malignant transformation of human breast epithelial cells with chemical carcinogens. Crit Rev Oncog 4:403–417PubMed

58.

Calaf G, Russo J (1993) Transformation of human breast epithelial cells by chemical carcinogens. Carcinogenesis 14:483–492PubMedCrossRef

59.

Caruso JA, Reiners JJ Jr, Emond J et al (2001) Genetic alteration of chromosome 8 is a common feature of human mammary epithelial cell lines transformed in vitro with benzo[a]pyrene. Mutat Res 473:85–99PubMed

60.

Naryan S, Jaiswal AS, Kang D et al (2004) Cigarette smoke condensate-induced transformation of normal human breast epithelial cells in vitro. Oncogene 23:5880–5889CrossRef

61.

Liu S, Lin YC (2004) Transformation of MCF-10A human breast epithelial cells by zeranol and estradiol-17beta. Breast J 10:514–521PubMedCrossRef

62.

Huggins C, Yang NC (1962) Induction and extinction of mammary cancer. A striking effect of hydrocarbons permits analysis of mechanisms of causes and cure of breast cancer. Science 137:257–262PubMedCrossRef

63.

Cavalieri E, Rogan E, Sinha D (1988) Carcinogenicity of aromatic hydrocarbons directly applied to rat mammary gland. J Cancer Res Clin Oncol 114:3–9PubMedCrossRef

64.

Oreffo VIC, Lin HW, Padmanabhan R, Witschi H (1993) K-ras and p53 point mutations in 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced hamster lung tumors. Carcinogenesis 14:451–455PubMedCrossRef

65.

Matzinger SA, Gunning WT, You M, Castonguay A (1994) Ki-ras mutations in 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-initiated and butylated hydroxytoluene-promoted lung tumors in A/J mice. Mol Carcinogenesis 11:42–48CrossRef

66.

Mehta RG (2000) Experimental basis for the prevention of breast cancer. Eur J Cancer 36:1275–1282PubMedCrossRef

Titel: Precancerous model of human breast epithelial cells induced by NNK for prevention
verfasst von: Nalin Siriwardhana
Shambhunath Choudhary
Hwa-Chain Robert Wang
Publikationsdatum: 01.06.2008
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 3/2008
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-007-9666-9

Springer Medizin

Precancerous model of human breast epithelial cells induced by NNK for prevention

Abstract

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2008

Fatty acid metabolism in breast cancer cells: differential inhibitory effects of epigallocatechin gallate (EGCG) and C75

Pre-administration of docetaxel protects against adriamycin-induced cardiotoxicity

NSAID use and breast cancer risk in the VITAL cohort

Parity and disparity in first course treatment of invasive breast cancer

Post-diagnosis statin use and breast cancer recurrence in a prospective cohort study of early stage breast cancer survivors

A randomized phase-III trial of docetaxel/capecitabine versus doxorubicin/cyclophosphamide as primary chemotherapy for patients with stage II/III breast cancer

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie