Analysis of cell cycle arrest and apoptosis induced by RCAS1.
A tumor-associated antigen RCAS1 (receptor binding cancer antigen expressed on SiSo cells) induces cell cycle arrest and apoptosis to a putative RCAS1 receptor (RCAS1-R) expressing cells such as T, B, and natural killer cells. Its expression is related with clinical poor prognosis of some malignant tumors. It is suggested that the expression of RCAS1 in tumor cells plays an important role in evasion from host immune system resulting tumor progression, invasion and metastasis. However, the mechanism of RCAS1 induced cell cycle arrest and apoptosis has not been clarified. In this study, we established a mouse L cell line transformed with tetracycline-induced rcas1 gene expression system and analyzed the RCAS1 functions. We showed that RCAS1 induced cytochrome c release and activation of caspase-3 for apoptosis. Moreover, we investigated cell cycle associated proteins and revealed that cyclin D3 decreased significantly and no change was seen in the expression levels of the other proteins. These results suggest that cyclin D3 is one of the key target molecules in the RCAS1-RCAS1-R signaling pathway.
Nishinakagawa
Takuya
T
Department of Immunological and Molecular Pharmacology, Faculty of Pharmaceutical Science, Fukuoka University, Fukuoka 814-0180, Japan.
Fujii
Sho
S
Nozaki
Tetsuya
T
Maeda
Tatsuhiro
T
Machida
Kazuyuki
K
Enjoji
Munechika
M
Nakashima
Manabu
M
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D048430:Cell Shape; D056743:Cyclin D3 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D051379:Mice
C099099:22-1-1 antigen; D000951:Antigens, Neoplasm; D018797:Cell Cycle Proteins; D056743:Cyclin D3; C534295:EBAG9 protein, mouse; D045304:Cytochromes c; D053148:Caspase 3