Expression of PRMT5 in lung adenocarcinoma and its significance in epithelial-mesenchymal transition.
Although protein arginine methyltransferase 5 (PRMT5) has been implicated in various cancers, its expression pattern in lung adenocarcinoma cell lines and tissues has not been elucidated enough. In this study, microarray analysis of 40 non-small-cell lung carcinoma cell lines showed that PRMT5 was a candidate histone methyltransferase gene that correlated with epithelial-mesenchymal transition. Immunocytochemical analysis of these cell lines indicated that the expression of PRMT5 was localized to the cytoplasm of E-cadherin-low and vimentin-high cell lines, whereas it was predominant in the nucleus and faint in the cytoplasm of E-cadherin-high and vimentin-low cell lines. Immunohistochemical analysis of lung adenocarcinoma cases (n = 130) revealed that the expression of PRMT5 was high in the cytoplasm of 47 cases (36%) and the nuclei of 34 cases (26%). The marked cytoplasmic expression of PRMT5 was frequently observed in high-grade subtypes (1 of 17 low grade, 21 of 81 intermediate grade, and 25 of 32 high grade; P < .0001) such as solid adenocarcinoma with the low expression of thyroid transcription factor 1 (the master regulator of lung) and low expression of cytokeratin 7 and E-cadherin (2 markers for bronchial epithelial differentiation), whereas the high nuclear expression of PRMT5 was frequently noted in adenocarcinoma in situ, a low-grade subtype (6 of 17 low grade, 25 of 81 intermediate grade, and 3 of 32 high grade; P = .0444). The cytoplasmic expression of PRMT5 correlated with a poor prognosis (P = .0089). We herein highlighted the importance of PRMT5 expression, especially its cytoplasmic expression, in the process of epithelial-mesenchymal transition and loss of the bronchial epithelial phenotype of lung adenocarcinoma.
Molecular Pathology Laboratory, Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
Reem
R
Ibrahim
Molecular Pathology Laboratory, Institute of Medical Science, the University of Tokyo, Tokyo, Japan; Department of Integrative Pathology, Jichi Medical University, Tochigi, Japan. Electronic address: vzv07574@nifty.com.
Daisuke
D
Matsubara
Molecular Pathology Laboratory, Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
Wael
W
Osman
Human Pathology Department, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
Teppei
T
Morikawa
Department of Cellular and Organ Pathology, Akita University Graduate School of Medicine, Akita, Japan.
Akiteru
A
Goto
Human Pathology Department, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
Shigeki
S
Morita
Human Pathology Department, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
Shumpei
S
Ishikawa
Division of Genome Science, Research Center for Advanced Science and Technology, the University of Tokyo, Tokyo, Japan.
Hiroyuki
H
Aburatani
Department of Clinical Laboratory, the University of Tokyo, Tokyo, Japan.
Daiya
D
Takai
Department of Thoracic Surgery, the University of Tokyo, Tokyo, Japan.
Jun
J
Nakajima
Human Pathology Department, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
Masashi
M
Fukayama
Department of Integrative Pathology, Jichi Medical University, Tochigi, Japan.
Toshiro
T
Niki
Molecular Pathology Laboratory, Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
Yoshinori
Y
Murakami
D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053552:Keratin-7 / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
D014408:Biomarkers, Tumor; D015820:Cadherins; D053552:Keratin-7; D014746:Vimentin; C400529:PRMT5 protein, human; D011484:Protein-Arginine N-Methyltransferases
EMT; Epigenetics; Lung adenocarcinoma; PRMT5