PT  - JOURNAL ARTICLE
AU  - TAKASHI TATARA
AU  - TORU MUKOHARA
AU  - RINA TANAKA
AU  - YOHEI SHIMONO
AU  - YOHEI FUNAKOSHI
AU  - YOSHINORI IMAMURA
AU  - MASANORI TOYODA
AU  - NAOMI KIYOTA
AU  - MIDORI HIRAI
AU  - YOSHIHIRO KAKEJI
AU  - HIRONOBU MINAMI
TI  - 3D Culture Represents Apoptosis Induced by Trastuzumab Better than 2D Monolayer Culture
DP  - 2018 May 01
TA  - Anticancer Research
PG  - 2831--2839
VI  - 38
IP  - 5
4099  - http://ar.iiarjournals.org/content/38/5/2831.short
4100  - http://ar.iiarjournals.org/content/38/5/2831.full
SO  - Anticancer Res2018 May 01; 38
AB  - Background: Our hypothesis was that three-dimensional (3D) culture better represents differential in vivo responses to trastuzumab between PIK3CA-wild-type (wt) and mutant (mt) cell lines than does two-dimensional (2D) culture. Materials and Methods: Apoptosis and cell signaling proteins were evaluated in response to trastuzumab with and without BKM120, a pan-phosphatidylinositol 3-kinase (PI3K) inhibitor, using western blot analysis of four breast cancer cell lines with human epidermal growth factor receptor 2 (HER2) amplification. Results: Increased expression of cleaved poly (ADP-ribose) polymerase (PARP) was observed only in 3D-cultured PIK3CA-wt lines in response to trastuzumab, but not in 2D-cultured PIK3CA-wt or PIK3CA-mt lines. Decrease in the ratio of phosphorylated (p-)AKT to AKT in response to trastuzumab was more profound in PIK3CA-wt cells than in PIK3CA-mt cells in 3D culture, while the difference between PIK3CA genotypes was less apparent in 2D culture. Treatment with BKM120 and trastuzumab resulted in a stronger increase in cleaved PARP than either treatment alone. Conclusion: 3D Culture appears to better represent trastuzumab-induced apoptosis and resistance to trastuzumab associated with PIK3CA mutation.