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Prognostic features of signal transducer and activator of transcription 3 in an ER(+) breast cancer model system.

Liu LY, Chang LY, Kuo WH, Hwa HL, Lin YS, Jeng MH, Roth DA, Chang KJ, Hsieh FJ - Cancer Inform (2014)

Bottom Line: These data predict malignant events, treatment responses and a novel enhancer of tamoxifen resistance.Taken together, we identify a poor prognosis relevant gene set within the STAT3 network and a robust one in a subset of patients.VEGFA, ABL1, LYN, IGF2R and STAT3 are suggested therapeutic targets for further study based upon the degree of differential expression in our model.

View Article: PubMed Central - PubMed

Affiliation: Department of Agronomy, Biometry Division, National Taiwan University, Taipei, Taiwan.

ABSTRACT
The aberrantly expressed signal transducer and activator of transcription 3 (STAT3) predicts poor prognosis, primarily in estrogen receptor positive (ER(+)) breast cancers. Activated STAT3 is overexpressed in luminal A subtype cells. The mechanisms contributing to the prognosis and/or subtype relevant features of STAT3 in ER(+) breast cancers are through multiple interacting regulatory pathways, including STAT3-MYC, STAT3-ERα, and STAT3-MYC-ERα interactions, as well as the direct action of activated STAT3. These data predict malignant events, treatment responses and a novel enhancer of tamoxifen resistance. The inferred crosstalk between ERα and STAT3 in regulating their shared target gene-METAP2 is partially validated in the luminal B breast cancer cell line-MCF7. Taken together, we identify a poor prognosis relevant gene set within the STAT3 network and a robust one in a subset of patients. VEGFA, ABL1, LYN, IGF2R and STAT3 are suggested therapeutic targets for further study based upon the degree of differential expression in our model.

No MeSH data available.


Related in: MedlinePlus

ANOVA tests and Venn diagram analyses for finding the main components of the STAT3 network.(A) shows a gene pool called STAT3 cluster, which is significantly associated with mitotic count (41TFs including STAT3 and ARNT). (B) demonstrates the gene pools, which include (1) the MYC and STAT3 overlapping network of the ER(+) IDCs with clinicopathologically significant (CS) and luminal A enriched and (2) the non-overlapping gene pools. (C) is a bar chart, which contains 10 bars for the number of probes identified in 10 clinical parameters and in the CS and luminal A enriched MYC and STAT3 overlapping network (6,579 probes), with bars displayed in an ascending order. (D) is a bar chart, which contains 12 bars for the number of probes identified in 12 signal transduction pathways that are also in the MYC and STAT3 overlapping network of the ER(+) IDCs, with bars displayed in an ascending order.
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f2-cin-13-2014-021: ANOVA tests and Venn diagram analyses for finding the main components of the STAT3 network.(A) shows a gene pool called STAT3 cluster, which is significantly associated with mitotic count (41TFs including STAT3 and ARNT). (B) demonstrates the gene pools, which include (1) the MYC and STAT3 overlapping network of the ER(+) IDCs with clinicopathologically significant (CS) and luminal A enriched and (2) the non-overlapping gene pools. (C) is a bar chart, which contains 10 bars for the number of probes identified in 10 clinical parameters and in the CS and luminal A enriched MYC and STAT3 overlapping network (6,579 probes), with bars displayed in an ascending order. (D) is a bar chart, which contains 12 bars for the number of probes identified in 12 signal transduction pathways that are also in the MYC and STAT3 overlapping network of the ER(+) IDCs, with bars displayed in an ascending order.

Mentions: There are 2,335 probes in the STAT3 cluster selected by the ANOVA test that are potential determining factors of mitotic count (Fig. 2A). Only 41 TFs and/or TF subunits are in this cluster, which includes STAT3 and ARNT (Fig. 2A). However, based upon mitotic count relevant STAT3 regulatory network, MYC but not ARNT is the target gene of STAT3 (Table S1.1 in Suppl. 1 of Additional file 1). Moreover, mitotic count relevant MYC regulatory network predicts that MYC regulates STAT3 but not ARNT (Table S1.2 in Suppl. 1 of Additional file 1). Data in Tables S1.5 and S1.8 in Suppl. 1 indentify STAT3 as the predicted target gene of MYC in both 90 A and 72 A cohorts.


Prognostic features of signal transducer and activator of transcription 3 in an ER(+) breast cancer model system.

Liu LY, Chang LY, Kuo WH, Hwa HL, Lin YS, Jeng MH, Roth DA, Chang KJ, Hsieh FJ - Cancer Inform (2014)

ANOVA tests and Venn diagram analyses for finding the main components of the STAT3 network.(A) shows a gene pool called STAT3 cluster, which is significantly associated with mitotic count (41TFs including STAT3 and ARNT). (B) demonstrates the gene pools, which include (1) the MYC and STAT3 overlapping network of the ER(+) IDCs with clinicopathologically significant (CS) and luminal A enriched and (2) the non-overlapping gene pools. (C) is a bar chart, which contains 10 bars for the number of probes identified in 10 clinical parameters and in the CS and luminal A enriched MYC and STAT3 overlapping network (6,579 probes), with bars displayed in an ascending order. (D) is a bar chart, which contains 12 bars for the number of probes identified in 12 signal transduction pathways that are also in the MYC and STAT3 overlapping network of the ER(+) IDCs, with bars displayed in an ascending order.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3921136&req=5

f2-cin-13-2014-021: ANOVA tests and Venn diagram analyses for finding the main components of the STAT3 network.(A) shows a gene pool called STAT3 cluster, which is significantly associated with mitotic count (41TFs including STAT3 and ARNT). (B) demonstrates the gene pools, which include (1) the MYC and STAT3 overlapping network of the ER(+) IDCs with clinicopathologically significant (CS) and luminal A enriched and (2) the non-overlapping gene pools. (C) is a bar chart, which contains 10 bars for the number of probes identified in 10 clinical parameters and in the CS and luminal A enriched MYC and STAT3 overlapping network (6,579 probes), with bars displayed in an ascending order. (D) is a bar chart, which contains 12 bars for the number of probes identified in 12 signal transduction pathways that are also in the MYC and STAT3 overlapping network of the ER(+) IDCs, with bars displayed in an ascending order.
Mentions: There are 2,335 probes in the STAT3 cluster selected by the ANOVA test that are potential determining factors of mitotic count (Fig. 2A). Only 41 TFs and/or TF subunits are in this cluster, which includes STAT3 and ARNT (Fig. 2A). However, based upon mitotic count relevant STAT3 regulatory network, MYC but not ARNT is the target gene of STAT3 (Table S1.1 in Suppl. 1 of Additional file 1). Moreover, mitotic count relevant MYC regulatory network predicts that MYC regulates STAT3 but not ARNT (Table S1.2 in Suppl. 1 of Additional file 1). Data in Tables S1.5 and S1.8 in Suppl. 1 indentify STAT3 as the predicted target gene of MYC in both 90 A and 72 A cohorts.

Bottom Line: These data predict malignant events, treatment responses and a novel enhancer of tamoxifen resistance.Taken together, we identify a poor prognosis relevant gene set within the STAT3 network and a robust one in a subset of patients.VEGFA, ABL1, LYN, IGF2R and STAT3 are suggested therapeutic targets for further study based upon the degree of differential expression in our model.

View Article: PubMed Central - PubMed

Affiliation: Department of Agronomy, Biometry Division, National Taiwan University, Taipei, Taiwan.

ABSTRACT
The aberrantly expressed signal transducer and activator of transcription 3 (STAT3) predicts poor prognosis, primarily in estrogen receptor positive (ER(+)) breast cancers. Activated STAT3 is overexpressed in luminal A subtype cells. The mechanisms contributing to the prognosis and/or subtype relevant features of STAT3 in ER(+) breast cancers are through multiple interacting regulatory pathways, including STAT3-MYC, STAT3-ERα, and STAT3-MYC-ERα interactions, as well as the direct action of activated STAT3. These data predict malignant events, treatment responses and a novel enhancer of tamoxifen resistance. The inferred crosstalk between ERα and STAT3 in regulating their shared target gene-METAP2 is partially validated in the luminal B breast cancer cell line-MCF7. Taken together, we identify a poor prognosis relevant gene set within the STAT3 network and a robust one in a subset of patients. VEGFA, ABL1, LYN, IGF2R and STAT3 are suggested therapeutic targets for further study based upon the degree of differential expression in our model.

No MeSH data available.


Related in: MedlinePlus