The online version of this article (doi:10.1186/1476-4598-11-90) contains supplementary material, which is available to authorized users.
All authors declare that they do not have any competing interests.
SK designed the study, partiscipated in carcinogenesis experiments, analyzed the data, preparing the figures and tables, and wrote a paper. JP and TK carried out carcinogenesis experiments, and prepared histological samples. MY prepared histological samples and performed immunohistochemistry. CV participated in designing carcinogenesis experiments, data analysis and interpretation of the results. JMW participated in designing carcinogenesis study, examined histological specimens, and analyzed the data and helped preparing the tables. All authors read and approved the final manuscript.
The CCAAT/enhancer binding proteins (C/EBPs) play important roles in carcinogenesis of many tumors including the lung. Since multiple C/EBPs are expressed in lung, the combinatorial expression of these C/EBPs on lung carcinogenesis is not known.
A transgenic mouse line expressing a dominant negative A-C/EBP under the promoter of lung epithelial Clara cell secretory protein (CCSP) gene in doxycycline dependent fashion was subjected to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung carcinogenesis bioassay in the presence and absence of doxycycline, and the effect of abolition of DNA binding activities of C/EBPs on lung carcinogenesis was examined.
A-C/EBP expression was found not to interfere with tumor development; however, it suppressed the malignant conversion of adenoma to carcinoma during NNK-induced lung carcinogenesis. The results suggested that Ki67 may be used as a marker for lung carcinomas in mouse.
The DNA binding of C/EBP family members can be used as a potential molecular target for lung cancer therapy.
Halmos B, Huettner CS, Kocher O, Ferenczi K, Karp DD, Tenen DG: Down-regulation and antiproliferative role of C/EBPalpha in lung cancer. Cancer Res. 2002, 62: 528-534. PubMed
Gombart AF, Hofmann WK, Kawano S, Takeuchi S, Krug U, Kwok SH, Larsen RJ, Asou H, Miller CW, Hoelzer D, Koeffler HP: Mutations in the gene encoding the transcription factor CCAAT/enhancer binding protein alpha in myelodysplastic syndromes and acute myeloid leukemias. Blood. 2002, 99: 1332-1340. 10.1182/blood.V99.4.1332 CrossRefPubMed
Shim M, Powers KL, Ewing SJ, Zhu S, Smart RC: Diminished expression of C/EBPalpha in skin carcinomas is linked to oncogenic Ras and reexpression of C/EBPalpha in carcinoma cells inhibits proliferation. Cancer Res. 2005, 65: 861-867. PubMed
Raught B, Gingras AC, James A, Medina D, Sonenberg N, Rosen JM: Expression of a translationally regulated, dominant-negative CCAAT/enhancer-binding protein beta isoform and up-regulation of the eukaryotic translation initiation factor 2alpha are correlated with neoplastic transformation of mammary epithelial cells. Cancer Res. 1996, 56: 4382-4386. PubMed
Tomita T, Kido T, Kurotani R, Iemura S, Sterneck E, Natsume T, Vinson C, Kimura S: CAATT/enhancer-binding proteins alpha and delta interact with NKX2-1 to synergistically activate mouse secretoglobin 3A2 gene expression. J Biol Chem. 2008, 283: 25617-25627. 10.1074/jbc.M805140200 PubMedCentralCrossRefPubMed
Kido T, Tomita T, Okamoto M, Cai Y, Matsumoto Y, Vinson C, Maru Y, Kimura S: FOXA1 plays a role in regulating secretoglobin 1a1 expression in the absence of CCAAT/enhancer binding protein activities in lung in vivo. Am J Physiol Lung Cell Mol Physiol. 2011, 300: L441-L452. 10.1152/ajplung.00435.2009 PubMedCentralCrossRefPubMed
Rucci N, Sanita P, Angelucci A: Roles of metalloproteases in metastatic niche. Curr Mol Medicine. 2011, 11: 609-622. 10.2174/156652411797536705. CrossRef
Rehm S, Ward JM, ten Have-Opbroek AA, Anderson LM, Singh G, Katyal SL, Rice JM: Mouse papillary lung tumors transplacentally induced by N-nitrosoethylurea: evidence for alveolar type II cell origin by comparative light microscopic, ultrastructural, and immunohistochemical studies. Cancer Res. 1988, 48: 148-160. PubMed
Aune G, Stunes AK, Tingulstad S, Salvesen O, Syversen U, Torp SH: The proliferation markers Ki-67/MIB-1, phosphohistone H3, and survivin may contribute in the identification of aggressive ovarian carcinomas. Internatl J Clinic Experi Pathol. 2011, 4: 444-453.
Vincent-Salomon A, Hajage D, Rouquette A, Cedenot A, Gruel N, Alran S, Sastre-Garau X, Sigal-Zafrani B, Fourquet A, Kirova Y: High Ki67 expression is a risk marker of invasive relapse for classical lobular carcinoma in situ patients. Breast. 2012, 21: 380-383. 10.1016/j.breast.2012.03.005 CrossRefPubMed
Fainaru O, Adini I, Benny O, Bazinet L, Pravda E, D'Amato R, Folkman J: Doxycycline induces membrane expression of VE-cadherin on endothelial cells and prevents vascular hyperpermeability. FASEB J: official publication of the Federation of American Societies for Experimental Biology. 2008, 22: 3728-3735. 10.1096/fj.08-110494. CrossRef
Nikitin AY, Alcaraz A, Anver MR, Bronson RT, Cardiff RD, Dixon D, Fraire AE, Gabrielson EW, Gunning WT, Haines DC, Kaufman MH, Linnoila RI, Maronpot RR, Rabson AS, Reddick RL, Rehm S, Rozengurt N, Schuller HM, Shmidt EN, Travis WD, Ward JM, Jacks T: Classification of proliferative pulmonary lesions of the mouse: recommendations of the mouse models of human cancers consortium. Cancer Res. 2004, 64: 2307-2316. 10.1158/0008-5472.CAN-03-3376 CrossRefPubMed
- Deficiency of CCAAT/enhancer binding protein family DNA binding prevents malignant conversion of adenoma to carcinoma in NNK-induced lung carcinogenesis in the mouse
Jerrold M Ward
- BioMed Central
Neu im Fachgebiet Onkologie
e.Med Kampagnen-Visual, Mail Icon II