title: Suppression of PTEN/AKT signaling decreases the expression of TUBB3 and TOP2A with subsequent inhibition of cell growth and induction of apoptosis in human breast cancer MCF-7 cells via ATP and caspase-3 signaling pathways.
abstract: The aim of the present study was to evaluate the effects of PTEN/AKT signaling on TUBB3 and TOP2A expression and on the subsequent cell growth of human breast cancer MCF-7 cells. We found that the disease-free survival (DFS) and overall survival (OS) of breast cancer patients with TUBB3‑positive tumors were lower than these rates in the patients with TUBB3-negative tumors. Meanwhile, DFS and OS of breast cancer patients with TOP2A-positive tumors were also lower than these rates in patients with TOP2A-negative tumors. Suppression of PTEN reduced the protein expression of TUBB3 and TOP2A in MCF-7 cells. Suppression of PTEN also reduced cell proliferation and induced apoptosis and caspase-3 activity in MCF-7 cells. Moreover, an increase in ATP also reduced TUBB3 and TOP2A protein expression, reduced cell proliferation and induced apoptosis and caspase-3 activity in the MCF-7 cells following suppression of PTEN. Suppression of phosphorylation-AKT (p-AKT) reduced the protein expression of TUBB3 and TOP2A in the MCF-7 cells. Suppression of p-AKT also reduced cell proliferation and induced apoptosis and caspase-3 activity in the MCF-7 cells. Then, ATP also reduced TUBB3 and TOP2A protein expression, reduced cell proliferation and induced apoptosis and caspase-3 activity in MCF-7 cells following suppression of p-AKT. These results suggest that PTEN/AKT signaling affects the expression of TUBB3 and TOP2A reducing cell growth and inducing apoptosis of human breast cancer MCF-7 cells through ATP and caspase-3 signaling pathways. TUBB3 and TOP2A may be promising prognostic markers for the efficacy of adjuvant cisplatin-based chemotherapy.
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, P.R. China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Medical Imaging Center, The First Affiliated Hospital of Jinan University, Guangzhou 510630, P.R. China.
authors.forename: Changzheng
authors.initials: C
authors.lastname: Shi
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, P.R. China.
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Surgery on Galactophore, The First Affiliated Hospital of Jinan University, Guangzhou 510630, P.R. China.
authors.forename: Rongzhao
authors.initials: R
authors.lastname: Lv
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, P.R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, P.R. China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D009942:Organometallic Compounds / Q000494:pharmacology; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000075223:Poly-ADP-Ribose Binding Proteins; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D014404:Tubulin / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; C494826:BAX protein, human; D004268:DNA-Binding Proteins; D009942:Organometallic Compounds; D000075223:Poly-ADP-Ribose Binding Proteins; C498585:TUBB3 protein, human; D014404:Tubulin; C000600334:VO-OHpic; D051028:bcl-2-Associated X Protein; D000255:Adenosine Triphosphate; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D053148:Caspase 3; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human