Differential gene signatures in rat mammary tumors induced by DMBA and those induced by fractionated gamma radiation.
The aim of this work was to identify specific genes involved in rat mammary tumors induced by dimethylbenz(a)anthracene (DMBA) or radiation. More TUNEL- and PCNA-positive cells were present in mammary tumors induced by radiation than in tumors induced by DMBA, whereas DNA damage responses like p53 accumulation and histone H2AX phosphorylation were higher in DMBA-induced tumors, even though the pathology was similar in both types of tumors. cDNA microarray and real-time RT-PCR analysis of radiation- or DMBA-induced tumor tissues, revealed that stanniocalcin 2 (Stc2), interferon regulatory factor 1 (Irf1), interleukin 18 binding protein (Il18bp), and chloride channel calcium activated 3 (Clca3) were expressed in both, and that arachidonate 5-lipoxygenase activating protein 1 (Alox5ap) and cathepsin S (Ctss) were expressed only in radiation-induced tumors. No DMBA-specific gene signatures were found. Soft agar growth assays were carried out to identify the carcinogenic features of these specific genes. Cells stably transfected with Alox5ap, Ctss, Stc2, Irf1, Il18bp and Clca3 showed morphological changes compared to controls. These findings indicate different gene alterations in carcinogen- or radiation-induced mammary tumors with similar pathological stages.
Lee
Hae-June
HJ
Division of Radiation Effect, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
Lee
Yoon-Jin
YJ
Kang
Chang-Mo
CM
Bae
Sangwoo
S
Jeoung
Dooil
D
Jang
Ja-June
JJ
Lee
Seung-Sook
SS
Cho
Chul-Koo
CK
Lee
Yun-Sil
YS
D058927:5-Lipoxygenase-Activating Proteins; D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D004249:DNA Damage; D019583:Dose Fractionation, Radiation; D005260:Female; D005720:Gamma Rays; D020869:Gene Expression Profiling; D006657:Histones / Q000032:analysis; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D058927:5-Lipoxygenase-Activating Proteins; C548592:ALOX5AP protein, human; C548594:Alox5ap protein, rat; D002352:Carrier Proteins; C468783:H2AX protein, human; D006657:Histones; D008565:Membrane Proteins; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D015127:9,10-Dimethyl-1,2-benzanthracene