2007 Fiscal Year Final Research Report Summary
Antitumor effects of monoclonal antibodies affecting dimerization between ErbB family members
| Project/Area Number |
18590088
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Biological pharmacy
|
|---|
| Research Institution | Setsunan University |
|---|
Principal Investigator |
ITO Fumiaki Setsunan University, DEPARTMENT OF BIOCHEMISTRY, PROFESSOR (80111764)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NISHIO Kazuto KINKI UNVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF GENOME BIOLOGY, PROFESSOR (10208134)
|
|---|
| Project Period (FY) |
2006 – 2007
|
| Keywords | EGF receptor / Monoclonal antibody therapy / Anti-cancer drugs / Tyrosine kinase inhibitors / Molecular targeting drugs / ErbB2 / ErbB3 / Non-small lung cancer |
|---|
| Research Abstract |
Epidermal growth factor receptor (EGFR) forms homodimers and heterodimers with the other ErbB family members, ErbB2, ErbB3, and ErbB4. ErbB family members play fundamental roles in cell growth and cell survival, and they are targets for monoclonal antibody (mAb) therapy of cancer, because inappropriate ErbB activity has been implicated in several human cancer cells. However, our understanding of the pharmacological effects of mAb on tumor growth is not well developed. In this study, we examined effects of our mAb against EGFR, designated as B4G7, on growth of human non-small cell lung cancer cell lines (PC-9, PC14, and A549) as well as on that of A431 human epidermoid carcinoma cells. B4G7, but not EGF, exhibited growth-stimulatory effect upon all of these human cancer cell lines. The B4G7-stimulated cell growth was not affected by AG1478, a specific inhibitor of EGFR tyrosine kinase. Thus, the growth stimulation by B4G7 appears to be independent of the activation of EGFR tyrosine kinase. Immunoprecipitation with anti-ErbB3 antibody revealed that B4G7, but not EGF, stimulated heterodimerization between ErbB2 and ErbB3. ErbB3 was tyrosine-phosphorylated in the presence of B4G7 but not in the presence of EGF. Further, the phosphorylation of ErbB3 and B4G7-induced increase in cell growth were inhibited by AG825, a specific inhibitor of ErbB2, indicating that the ErbB2/ErbB3 dimer functions to promote cell growth in B4G7-treated cells. These findings show that ErbB family members other than EGFR affect sensitivity to EGFR-directed antibody therapies for cancer. Examination of expression levels of ErbB2 and ErbB3 in cancer cells is of importance in optimizing EGFR family-directed therapies for cancer.
|
-
-
[Journal Article] 「研究成果報告書概要(欧文)」より2007
Author(s)
Mari Maegawa, Kenji Takeuchi, Eishi Funakoshi, Katsumi Kawasaki, Kazuto Nishio, Nobuyoshi Shimizu, Fumiaki Ito
-
Journal Title
Mol Cancer Res 5-4
Pages: 393-401
-
-
-
-
-
-
-
-
-
-
-
[Presentation] A novel signaling pathway of deletional mutant EGFR2007
Author(s)
Mari Maegawa, HideyukiYokote, Kazuko Matsumoto, Kaoru Tanaka, Hiroyasu Kaneda, Yoshihiko Fujita, Marco De Verasco, Tokuzo Arao, Fumiaki Koizumi, Fumiaki Ito, Kazuto Nishio
Organizer
66th Annual Meeting of the Japanese Cancer Association
Place of Presentation
Yokohama
Year and Date
2007-10-05
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
-
-
-
-
-
