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Breast cancer genes PSMC3IP and EPSTI1 play a role in apoptosis regulation.

Capdevila-Busquets E, Badiola N, Arroyo R, Alcalde V, Soler-López M, Aloy P - PLoS ONE (2015)

Bottom Line: A key element to delineate the biology of individual tumors is the regulation of apoptosis.We first explore the existence of direct physical interactions with annotated BC-apoptotic genes.Our results show that PSMC3IP and EPSTI1 are able to modulate the extrinsic apoptotic pathway in estrogen receptor positive and triple negative breast cancer cell lines, highlighting them as potential therapeutic targets.

View Article: PubMed Central - PubMed

Affiliation: Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Catalonia, Spain.

ABSTRACT
A key element to delineate the biology of individual tumors is the regulation of apoptosis. In this work, we functionally characterize two breast cancer associated genes, the proteasome 26S subunit ATPase 3 interacting protein (PSMC3IP) and the epithelial-stromal interaction 1 (EPSTI1), to explore their potential apoptotic role in breast cancer. We first explore the existence of direct physical interactions with annotated BC-apoptotic genes. Based on the generated interaction network, we examine several apoptotic markers to determine the effect of PSMC3IP and EPSTI1 gene expression modulation in two different human breast cancer cell lines to suggest potential molecular mechanisms to unveil their role in the disease. Our results show that PSMC3IP and EPSTI1 are able to modulate the extrinsic apoptotic pathway in estrogen receptor positive and triple negative breast cancer cell lines, highlighting them as potential therapeutic targets.

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Expression of PSMC3IP and EPSTI1 in normal and breast cancer cell lines.We inspected the endogenous expression of PSMC3IP (A) and EPSTI1 (B) in two types of breast cancer cell lines, MDA-MB-231 and MCF-7, as compared to a normal breast epithelial cell line, MCF-10A. Estimated protein levels based on densitometry (right) of the immunoblots (left) show a PSMC3IP 19- and 15-fold expression in MDA-MB-231 and MCF-7 cells, while EPSTI1 only shows 1.9- and 1.3-fold in each cell line, respectively. Protein levels were normalized based on the loading control protein β-actin. (*P <0.05, **P<0.01, ***P <0.001 vs MCF-10A cells).
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pone.0115352.g001: Expression of PSMC3IP and EPSTI1 in normal and breast cancer cell lines.We inspected the endogenous expression of PSMC3IP (A) and EPSTI1 (B) in two types of breast cancer cell lines, MDA-MB-231 and MCF-7, as compared to a normal breast epithelial cell line, MCF-10A. Estimated protein levels based on densitometry (right) of the immunoblots (left) show a PSMC3IP 19- and 15-fold expression in MDA-MB-231 and MCF-7 cells, while EPSTI1 only shows 1.9- and 1.3-fold in each cell line, respectively. Protein levels were normalized based on the loading control protein β-actin. (*P <0.05, **P<0.01, ***P <0.001 vs MCF-10A cells).

Mentions: We first investigated whether PSMC3IP and EPSTI1 endogenous protein levels are indeed up-regulated in carcinoma cells such as MCF-7 and MDA-MB-231 (Fig. 1), which represent common breast cancer subtypes differently graded upon hormone dependency and aggressiveness. MCF-7 is a weakly invasive luminal cell line, representative of estrogen receptor (ER)-positive tumors [34]. On the other hand, MDA-MB-231 is a highly invasive basal cell line, and it is often used as model for ER-negative tumors [35]. PSMC3IP is highly overexpressed in both MDA-MB-231 and MCF-7, respectively, compared to the non-tumorigenic breast cancer cell line (MCF-10A) (Fig. 1A). Conversely, EPSTI1 shows a more moderate increase, particularly in MCF-7 cells (1.3-fold, Fig. 1B), as previously observed [17], providing evidence about the heteroclonal nature of MCF-7 sublines [36].


Breast cancer genes PSMC3IP and EPSTI1 play a role in apoptosis regulation.

Capdevila-Busquets E, Badiola N, Arroyo R, Alcalde V, Soler-López M, Aloy P - PLoS ONE (2015)

Expression of PSMC3IP and EPSTI1 in normal and breast cancer cell lines.We inspected the endogenous expression of PSMC3IP (A) and EPSTI1 (B) in two types of breast cancer cell lines, MDA-MB-231 and MCF-7, as compared to a normal breast epithelial cell line, MCF-10A. Estimated protein levels based on densitometry (right) of the immunoblots (left) show a PSMC3IP 19- and 15-fold expression in MDA-MB-231 and MCF-7 cells, while EPSTI1 only shows 1.9- and 1.3-fold in each cell line, respectively. Protein levels were normalized based on the loading control protein β-actin. (*P <0.05, **P<0.01, ***P <0.001 vs MCF-10A cells).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4295872&req=5

pone.0115352.g001: Expression of PSMC3IP and EPSTI1 in normal and breast cancer cell lines.We inspected the endogenous expression of PSMC3IP (A) and EPSTI1 (B) in two types of breast cancer cell lines, MDA-MB-231 and MCF-7, as compared to a normal breast epithelial cell line, MCF-10A. Estimated protein levels based on densitometry (right) of the immunoblots (left) show a PSMC3IP 19- and 15-fold expression in MDA-MB-231 and MCF-7 cells, while EPSTI1 only shows 1.9- and 1.3-fold in each cell line, respectively. Protein levels were normalized based on the loading control protein β-actin. (*P <0.05, **P<0.01, ***P <0.001 vs MCF-10A cells).
Mentions: We first investigated whether PSMC3IP and EPSTI1 endogenous protein levels are indeed up-regulated in carcinoma cells such as MCF-7 and MDA-MB-231 (Fig. 1), which represent common breast cancer subtypes differently graded upon hormone dependency and aggressiveness. MCF-7 is a weakly invasive luminal cell line, representative of estrogen receptor (ER)-positive tumors [34]. On the other hand, MDA-MB-231 is a highly invasive basal cell line, and it is often used as model for ER-negative tumors [35]. PSMC3IP is highly overexpressed in both MDA-MB-231 and MCF-7, respectively, compared to the non-tumorigenic breast cancer cell line (MCF-10A) (Fig. 1A). Conversely, EPSTI1 shows a more moderate increase, particularly in MCF-7 cells (1.3-fold, Fig. 1B), as previously observed [17], providing evidence about the heteroclonal nature of MCF-7 sublines [36].

Bottom Line: A key element to delineate the biology of individual tumors is the regulation of apoptosis.We first explore the existence of direct physical interactions with annotated BC-apoptotic genes.Our results show that PSMC3IP and EPSTI1 are able to modulate the extrinsic apoptotic pathway in estrogen receptor positive and triple negative breast cancer cell lines, highlighting them as potential therapeutic targets.

View Article: PubMed Central - PubMed

Affiliation: Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Catalonia, Spain.

ABSTRACT
A key element to delineate the biology of individual tumors is the regulation of apoptosis. In this work, we functionally characterize two breast cancer associated genes, the proteasome 26S subunit ATPase 3 interacting protein (PSMC3IP) and the epithelial-stromal interaction 1 (EPSTI1), to explore their potential apoptotic role in breast cancer. We first explore the existence of direct physical interactions with annotated BC-apoptotic genes. Based on the generated interaction network, we examine several apoptotic markers to determine the effect of PSMC3IP and EPSTI1 gene expression modulation in two different human breast cancer cell lines to suggest potential molecular mechanisms to unveil their role in the disease. Our results show that PSMC3IP and EPSTI1 are able to modulate the extrinsic apoptotic pathway in estrogen receptor positive and triple negative breast cancer cell lines, highlighting them as potential therapeutic targets.

Show MeSH
Related in: MedlinePlus