Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Induction of apoptosis by DNA-damaging agents involves the activation of mitochondrial apoptotic pathway. Aven has been identified as an antiapoptotic protein and has been shown to activate ATM in response to DNA damage. In this study, we demonstrated that enforced expression of Aven blocks UV-irradiation-, SN-38- or cisplatin-induced apoptosis upstream of mitochondria by stabilising Bcl-xL protein levels in breast cancer cells. Aven silencing by RNA interference markedly enhanced apoptotic response following treatment with DNA-damaging agents. Aven is complexed with Bcl-xL in untreated breast cancer cells and treatment with DNA-damaging agents led to decreased Aven/Bcl-xL interaction. Importantly, Bcl-xL was necessary for the prosurvival activity of Aven and depletion of Bcl-xL abrogated Aven-mediated protection against DNA damage-induced apoptosis. Analysis of breast cancer tissue microarrays revealed decreased Aven nuclear expression in breast cancer tissues compared with non-neoplastic breast tissues. In particular, we detected reduced nuclear expression of Aven in infiltrating ductal carcinoma and papillary carcinoma breast cancer subtypes compared with non-neoplastic breast tissues and infiltrating lobular breast cancer tissues. Our results suggest that Aven is an important mediator in DNA damage-induced apoptotic signalling in breast cancer cells and its nuclear expression is altered in breast cancer tissues, which may contribute to genomic instability in breast cancer tumours.
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PMID:Aven blocks DNA damage-induced apoptosis by stabilising Bcl-xL. 2061 36

Metaplastic breast carcinoma (MBC) is a rare subtype of breast cancer with variable morphology. MBC is more often triple negative (ER-, PR-, HER2-) and is associated with poorer clinical outcome when compared with infiltrating ductal carcinoma. The purpose of our study is to identify molecular alterations in MBC using next-generation sequencing (NGS), which may aid chemotherapy selection and use of targeted therapy. A cohort of 18 patients with MBC yielded adequate DNA from microdissected formalin-fixed and paraffin-embedded tumor blocks. NGS was performed using the Ion AmpliSeq cancer hotspot mutation panel version 2 kit, which targets hotspot regions in 50 genes. Immunohistochemical stains for androgen receptor (AR), and programmed cell death ligand-1 were performed. A total of 23 genetic alterations were identified in 15 (83.3%) of 18 patients. Eleven genetic alterations in the PI3K signaling pathway were identified in 9 (50.0%) of 18 patients, including 7 PIK3CA mutations (38.9%), 3 PTEN genetic alterations (16.7%), and 1 AKT1 mutation (5.6%). Ten (55.6%) of 18 patients each harbored 1 TP53 genetic alteration. Additional genetic alterations identified were 1 HRAS mutation and 1 ATM mutation. AR immunoreactivity was identified in 2 (11.1%) of 18 patients. Programmed cell death ligand-1 was negative in all patients. NGS analysis demonstrated that PI3K pathway-related genetic alterations were detected in a high percentage of MBCs, suggesting that targeting the PI3K/mTOR pathway may be promising in patients with MBC. In addition, patients with AR expressing MBC may benefit from androgen antagonist treatment.
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PMID:Molecular characterization of metaplastic breast carcinoma via next-generation sequencing. 3053 93