FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2740756479> ?p ?o ?g. }

• W2740756479 abstract "Basal-like 2 (BL2) triple negative breast cancer (TNBC) is an aggressive molecular subtype of breast cancer with a poor clinical outcome. These cancers are characterized by overexpression of epidermal growth factor receptor (EGFR), loss of PTEN protein expression, and presence of mutated TP53. Despite overexpression of EGFR, EGFR-targeted therapies have performed poorly in clinical settings. Therefore, understanding the mechanisms of resistance in these cells is critical for improved patient care. To understand the oncogenic signaling landscape in BL2 TNBC, our lab utilizes the BL2 cell lines SUM-149 and SUM-229, which overexpress EGFR activated by an amphiregulin-mediated autocrine loop, and are PTEN null. In addition, we utilize the BL1 subtype cell line MDA-MB-468, which also exhibits overexpression of EGFR and loss of PTEN. Both the BL1 and BL2 cell lines exhibit elevated levels of phosphorylated AKT (p-AKT) compared to control MCF-10A cells. However, while treatment of SUM-149 and SUM-229 cells with inhibitors targeting EGFR (Gefitinib), type-1 PI3K (BKM120, BKM), mTOR (KU-0063794, KU) and pan-AKT (MK2206, MK) did not reduce p-AKT levels, MCF-10A and MDA-MB-468 cell lines treated with the same panel of targeted inhibitors showed marked inhibition of p-AKT. In addition, re-expression of PTEN in SUM-149 and SUM-229 cells had little effect on p-AKT but dramatically reduced p-AKT in MDA-MB-468 cells. Although PTEN re-expression alone had little effect on p-AKT in SUM-149 and SUM-229 cells, these cells did display decreased AKT phosphorylation following treatment with Gefitinib, BKM, KU, and MK. There are three isoforms of AKT (AKT1, AKT2 and AKT3) of which, AKT3 has been implicated in the aggressive nature of some cancers. Previous studies in our lab showed that SUM-149 and SUM-229 cell lines have higher levels of AKT3 message and protein compared to the other AKT isoforms. AKT3 expression was also higher in the BL2 cell lines compared to BL1 and control cells. This differential expression of AKT isoforms led us to examine the impact of AKT isoform-specific signaling. Using PTEN re-expressing SUM-149 cells, we showed that PTEN re-expression resulted in decreased phosphorylation of AKT1 but not of AKT3. However, PTEN re-expression combined with Gefitinib treatment dramatically reduced phosphorylation of both AKT1 and AKT3. Interestingly, while neither re-expression of PTEN nor Gefitinib expression alone had an effect on colony-forming efficiency, PTEN re-expression coupled with Gefitinib treatment was able to reduce colony formation efficiency in both SUM-149 and SUM-229 cell lines. Taken together, these data indicate that BL2 breast cancers, with overexpression of EGFR and loss of PTEN expression, have an oncogenic signaling network involving AKT3 that contributes to the aggressive and drug-resistant phenotype observed in this subset of TNBC. Citation Format: Ericka L. Smith, Christiana S. Kappler, Stephen P. Ethier. Role of PTEN loss in basal-like 2 triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1339. doi:10.1158/1538-7445.AM2017-1339" @default.
• W2740756479 created "2017-08-08" @default.
• W2740756479 creator A5012150633 @default.
• W2740756479 creator A5057594429 @default.
• W2740756479 creator A5083579518 @default.
• W2740756479 date "2017-07-01" @default.
• W2740756479 modified "2023-09-26" @default.
• W2740756479 title "Abstract 1339: Role of PTEN loss in basal-like 2 triple negative breast cancer" @default.
• W2740756479 doi "https://doi.org/10.1158/1538-7445.am2017-1339" @default.
• W2740756479 hasPublicationYear "2017" @default.
• W2740756479 type Work @default.
• W2740756479 sameAs 2740756479 @default.
• W2740756479 citedByCount "1" @default.
• W2740756479 countsByYear W27407564792019 @default.
• W2740756479 crossrefType "proceedings-article" @default.
• W2740756479 hasAuthorship W2740756479A5012150633 @default.
• W2740756479 hasAuthorship W2740756479A5057594429 @default.
• W2740756479 hasAuthorship W2740756479A5083579518 @default.
• W2740756479 hasConcept C121608353 @default.
• W2740756479 hasConcept C126322002 @default.
• W2740756479 hasConcept C185592680 @default.
• W2740756479 hasConcept C2777609662 @default.
• W2740756479 hasConcept C2779438470 @default.
• W2740756479 hasConcept C2780110267 @default.
• W2740756479 hasConcept C2780580887 @default.
• W2740756479 hasConcept C502942594 @default.
• W2740756479 hasConcept C530470458 @default.
• W2740756479 hasConcept C54355233 @default.
• W2740756479 hasConcept C62478195 @default.
• W2740756479 hasConcept C71924100 @default.
• W2740756479 hasConcept C75217442 @default.
• W2740756479 hasConcept C81885089 @default.
• W2740756479 hasConcept C86554907 @default.
• W2740756479 hasConcept C86803240 @default.
• W2740756479 hasConcept C95444343 @default.
• W2740756479 hasConceptScore W2740756479C121608353 @default.
• W2740756479 hasConceptScore W2740756479C126322002 @default.
• W2740756479 hasConceptScore W2740756479C185592680 @default.
• W2740756479 hasConceptScore W2740756479C2777609662 @default.
• W2740756479 hasConceptScore W2740756479C2779438470 @default.
• W2740756479 hasConceptScore W2740756479C2780110267 @default.
• W2740756479 hasConceptScore W2740756479C2780580887 @default.
• W2740756479 hasConceptScore W2740756479C502942594 @default.
• W2740756479 hasConceptScore W2740756479C530470458 @default.
• W2740756479 hasConceptScore W2740756479C54355233 @default.
• W2740756479 hasConceptScore W2740756479C62478195 @default.
• W2740756479 hasConceptScore W2740756479C71924100 @default.
• W2740756479 hasConceptScore W2740756479C75217442 @default.
• W2740756479 hasConceptScore W2740756479C81885089 @default.
• W2740756479 hasConceptScore W2740756479C86554907 @default.
• W2740756479 hasConceptScore W2740756479C86803240 @default.
• W2740756479 hasConceptScore W2740756479C95444343 @default.
• W2740756479 hasLocation W27407564791 @default.
• W2740756479 hasOpenAccess W2740756479 @default.
• W2740756479 hasPrimaryLocation W27407564791 @default.
• W2740756479 hasRelatedWork W1601243762 @default.
• W2740756479 hasRelatedWork W1617918484 @default.
• W2740756479 hasRelatedWork W1991454630 @default.
• W2740756479 hasRelatedWork W1992367938 @default.
• W2740756479 hasRelatedWork W2033221202 @default.
• W2740756479 hasRelatedWork W2054145820 @default.
• W2740756479 hasRelatedWork W2074541871 @default.
• W2740756479 hasRelatedWork W2080205610 @default.
• W2740756479 hasRelatedWork W2160043536 @default.
• W2740756479 hasRelatedWork W2315122280 @default.
• W2740756479 hasRelatedWork W2359551929 @default.
• W2740756479 hasRelatedWork W2394648674 @default.
• W2740756479 hasRelatedWork W2489996284 @default.
• W2740756479 hasRelatedWork W2543795704 @default.
• W2740756479 hasRelatedWork W2561906708 @default.
• W2740756479 hasRelatedWork W2606795521 @default.
• W2740756479 hasRelatedWork W2625442338 @default.
• W2740756479 hasRelatedWork W2740366217 @default.
• W2740756479 hasRelatedWork W2904881544 @default.
• W2740756479 hasRelatedWork W3103949121 @default.
• W2740756479 isParatext "false" @default.
• W2740756479 isRetracted "false" @default.
• W2740756479 magId "2740756479" @default.
• W2740756479 workType "article" @default.