Extracellular signal-regulated protein kinase is activated in cervical intraepithelial neoplasms but inactivated in invasive cervical carcinoma.
The extracellular signal-regulated protein kinase (ERK) signaling pathway has been reported to play important roles in cell growth in various neoplasms. The purpose of the present study was to immunohistochemically analyze the phosphorylation status (activity) of ERK in 24 cases of cervical carcinoma using an antiphosphorylated ERK antibody (alphap-ERK Ab) that specifically recognizes the phosphorylated form of ERK (p-ERK). In normal cervical epithelium, p-ERK was found to be confined to basal cells that were negative for Ki-67, suggesting that ERK was not activated in proliferating normal cervical epithelium. In cervical intraepithelial neoplasms (CIN), increased abnormal parabasal cells were positive for both p-ERK and Ki-67, suggesting that ERK activation in CIN may be involved in tumor cell proliferation. In contrast, it was found that, in invasive cervical carcinomas, almost all the carcinoma cells were positive for Ki-67 but negative for p-ERK, suggesting that, in contrast to many other types of cancers, the ERK signaling pathway is downregulated in invasive cervical carcinoma. These findings suggest that the phosphorylation status of ERK differs between CIN and invasive carcinomas, and that downregulation of the ERK signaling pathway may contribute to transformation of CIN to invasive cervical carcinomas.
Matsuura
Keiko
K
Department of Molecular Pathology, Faculty of Medicine, Oita University, Yufu, Oita, Japan. matsuura@med.oita-u.ac.jp
Nohno
Yuka
Y
Hijiya
Naoki
N
Uchida
Tomohisa
T
Tsukamoto
Yoshiyuki
Y
Moriyama
Masatsugu
M
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002277:Carcinoma / Q000201:enzymology* / Q000473:pathology; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D004789:Enzyme Activation; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology; D010766:Phosphorylation; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000201:enzymology* / Q000473:pathology
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3