title: PTEN insufficiency modulates ER+ breast cancer cell cycle progression and increases cell growth in vitro and in vivo.
abstract: Phosphatase and tensin homolog (PTEN), a well-known tumor suppressor gene and frequently mutated or lost in breast cancer, possesses the negative regulation function over the PI3K/Akt/mTOR pathway. PTEN insufficiency has been associated with advanced breast cancer and poor prognosis of breast cancer patients. Recently, target therapies aimed at PI3K/Akt/mTOR pathway to treat breast cancer have got popularity. However, the exact effect of PTEN on breast cancer cells is still not well understood. This study demonstrated that PTEN knockdown in MCF-7 cells strengthened the downstream gene expressions, including p-Akt, p-ERK1/2, p-mTOR, p-p70s6k, and p-GSK3β. PTEN knockdown MCF-7 cells had increased cell growth and Ki-67 expression. Further Western blot demonstrated that p27 was repressed obviously with p21 slightly inhibited and CDK1, 2, 4, 6, cyclin A, and Cdc25C were upregulated in MCF-7 PTEN knockdown cells, leading to the higher growth rate. More importantly, PTEN knockdown MCF-7 cells had higher tumorigenesis and tumor growth in vivo. From our current work, we provided more detailed PTEN-mediated mechanisms to stimulate ER+ breast cancer cell growth. Our result may pave the way for further target therapy development used alone or in combination with other drugs for ER+ breast cancer with PTEN insufficiency.
authors: Department of General Surgery, Chang Gung Memorial Hospital, Chang Gung University, Keelung, Republic of China ; Department of General Surgery, Chang Gung University, Keelung, Taiwan, Republic of China.
authors: Kun-Chun
authors: KC
authors: Chiang
authors: Department of General Surgery, Chang Gung Memorial Hospital, Chang Gung University, Keelung, Republic of China.
authors: Huang-Yang
authors: HY
authors: Chen
authors: Department of Anatomy, Chang Gung University, Keelung, Taiwan, Republic of China.
authors: Shu-Yuan
authors: SY
authors: Hsu
authors: Graduate Institute of Clinical Medical Sciences, Chang Gung University, Keelung, Taiwan, Republic of China.
authors: Jong-Hwei S
authors: JH
authors: Pang
authors: Department of General Surgery, Chang Gung University, Keelung, Taiwan, Republic of China.
authors: Shang-Yu
authors: SY
authors: Wang
authors: Department of General Surgery, Chang Gung University, Keelung, Taiwan, Republic of China.
authors: Jun-Te
authors: JT
authors: Hsu
authors: Department of General Surgery, Chang Gung University, Keelung, Taiwan, Republic of China.
authors: Ta-Sen
authors: TS
authors: Yeh
authors: Department of Gastroenterology, Chang Gung University, Keelung, Taiwan, Republic of China.
authors: Li-Wei
authors: LW
authors: Chen
authors: Department of Endocrinology and Metabolism, Chang Gung University, Keelung, Taiwan, Republic of China.
authors: Sheng-Fong
authors: SF
authors: Kuo
authors: Department of Ophthalmology, Chang Gung Memorial Hospital, Chang Gung University, Keelung, Taiwan, Republic of China.
authors: Chi-Chin
authors: CC
authors: Sun
authors: Department of General Surgery, Chang Gung Memorial Hospital, Chang Gung University, Keelung, Republic of China.
authors: Jim-Ming
authors: JM
authors: Lee
authors: Department of General Surgery, Chang Gung University, Keelung, Taiwan, Republic of China.
authors: Chun-Nan
authors: CN
authors: Yeh
authors: Department of Anatomy, Chang Gung University, Keelung, Taiwan, Republic of China.
authors: Horng-Heng
authors: HH
authors: Juang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D061986:MCF-7 Cells; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D051059:PTEN Phosphohydrolase / Q000172:deficiency* / Q000235:genetics; D034622:RNA Interference; D011960:Receptors, Estrogen / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D047368:Tumor Burden
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D011960:Receptors, Estrogen; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: MCF-7; PTEN; breast cancer; cell cycle; target therapy; tumor growth