Up-regulation of growth factor receptor-bound protein 10 in cervical squamous cell carcinoma.
The Grb10 gene on chromosome 7p11.2-p12 belongs to a family of adapter proteins known to interact with a number of receptor tyrosine kinases, such as EGF, ErbB2/Her2, platelet-derived growth factor (PDGF), IGF-I receptors and vascular endothelial growth factor (VEGF) receptor, KDR (kinase insert domain containing receptor). In addition to receptor tyrosine kinases, Grb10 has also been found to interact with non-receptor tyrosine kinases such as Tec and Bcr-Abl, other cellular signaling molecules such as Raf-1, and the mitogen-activated protein (MAP) kinase, MEK. We demonstrated increased expression of Grb10 mRNA in more than one half of primary cervical squamous cell cancers (12 of 15 cases) when compared to corresponding non-cancerous uterine squamous cell tissues. In addition, immunohistochemical staining demonstrated that the Grb10 protein was prominent in the cytoplasm of cancer cells, whereas it was unreactive in the surrounding normal cervical squamous cells. In addition, its interruption by siRNA exhibited marked cell growth inhibition. These data indicate that amplification and increased expression of the Grb10 gene may play a role in the development of a portion of human cervical squamous cell cancer.
Okino
Keiko
K
Department of Obstetrics and Gynecology, Nippon Medical School, Bunkyo-ku, Tokyo 113-8602, Japan. k-ocky@nms.ac.jp
Konishi
Hideki
H
Doi
Daisuke
D
Yoneyama
Koichi
K
Ota
Yujiro
Y
Jin
Enjing
E
Kawanami
Oichi
O
Takeshita
Toshiyuki
T
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002584:Cervix Uteri / Q000378:metabolism / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D051383:GRB10 Adaptor Protein; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology
D011506:Proteins; D012333:RNA, Messenger; D051383:GRB10 Adaptor Protein; D066246:ErbB Receptors