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Gene expression profiling during rat mammary carcinogenesis induced by 7,12‐dimethylbenz[a]anthracene
Author(s) -
Souda Masakazu,
Umekita Yoshihisa,
Abeyama Kazuhiro,
Yoshida Hiroki
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24396
Subject(s) - dmba , laser capture microdissection , 7,12 dimethylbenz[a]anthracene , carcinogenesis , ductal carcinoma , biology , microdissection , cancer research , gene expression , immunohistochemistry , pathology , microbiology and biotechnology , breast cancer , gene , medicine , cancer , immunology , genetics
7,12‐Dimethylbenz[a]anthracene (DMBA)‐induced rat mammary carcinoma is a well‐recognized model; however, the genetic alterations during its carcinogenesis have yet to be determined. We used laser capture microdissection to specifically isolate cells from terminal end buds (TEBs), the origin of carcinoma, at 2 weeks after sesame oil treatment (control) or DMBA treatment (DMBA‐TEBs), ductal carcinoma in situ (DCIS) and invasive mammary carcinoma (MC). Using an oligonucleotide microarray representing 20,600 rat probe sequences, we analyzed gene expression profiles and validated mRNA and protein levels of genes of interest byreal‐time quantitative PCR and immunohistochemistry. The number of differentially expressed genes dramatically increased from DMBA‐TEBs (63) to DCIS (798) and MC (981). Only the expression of PEP‐19, an anti‐apoptotic gene, showed significant increases in DMBA‐TEBs (4‐fold), DCIS (10‐fold) and MC (16‐fold). MMP‐13 expression was increased markedly in DCIS (19‐fold) and MC (61‐fold) while OPN expression was increased 6‐fold in DCIS and 8‐fold in MC. MMP‐7 expression was increased 4‐fold in MC. Nidogen‐1; a participant in the assembly of basement membranes, TSP‐2; an inhibitor of angiogenesis and COUP‐TFI; a transcription repressor showed significant decreases in DCIS (4‐, 9‐ and 17‐fold, respectively) and MC (10‐, 37‐ and 100‐fold). Network analyses with IPA software revealed that the most significant network included Akt groups in DCIS and ERK groups in MC. The present findings provide us with a better understanding of the molecular alteration that occur during mammary carcinogenesis and suggest the importance of PEP‐19 overexpression in the very early stage of mammary carcinogenesis. © 2009 UICC