Limits...
By promoting cell differentiation, miR-100 sensitizes basal-like breast cancer stem cells to hormonal therapy.

Petrelli A, Carollo R, Cargnelutti M, Iovino F, Callari M, Cimino D, Todaro M, Mangiapane LR, Giammona A, Cordova A, Montemurro F, Taverna D, Daidone MG, Stassi G, Giordano S - Oncotarget (2015)

Bottom Line: Moreover, miR-100 favors BrCSC differentiation, converting a basal like phenotype into luminal.It induces the expression of a functional estrogen receptor (ER) and renders basal-like BrCSCs responsive to hormonal therapy.Our findings indicate a new possible therapeutic strategy, which could make aggressive breast cancers responsive to standard treatments.

View Article: PubMed Central - PubMed

Affiliation: University of Torino School of Medicine, Candiolo Cancer Institute-FPO, IRCCS, Str. Provinciale, Candiolo, Torino, Italy.

ABSTRACT
Basal-like breast cancer is an aggressive tumor subtype with a poor response to conventional therapies. Tumor formation and relapse are sustained by a cell subset of Breast Cancer Stem Cells (BrCSCs). Here we show that miR-100 inhibits maintenance and expansion of BrCSCs in basal-like cancer through Polo-like kinase1 (Plk1) down-regulation. Moreover, miR-100 favors BrCSC differentiation, converting a basal like phenotype into luminal. It induces the expression of a functional estrogen receptor (ER) and renders basal-like BrCSCs responsive to hormonal therapy. The key role played by miR-100 in breast cancer free-survival is confirmed by the analysis of a cohort of patients' tumors, which shows that low expression of miR-100 is a negative prognostic factor and is associated with gene signatures of high grade undifferentiated tumors. Our findings indicate a new possible therapeutic strategy, which could make aggressive breast cancers responsive to standard treatments.

Show MeSH

Related in: MedlinePlus

MiR-100 expression increases upon basal-like Breast Cancer Stem Cell (BrCSC) differentiationA, miR-100 expression in BrCSCs derived from human breast tumors evaluated by TaqMan RT-PCR. MiR-100 expression is reported as fold changes compared to P1. P1-P4: luminal; P5-P8: basal-like. B, miR-100 expression in basal-like BrCSCs (P5) before and after growth in differentiation condition, at the indicated times. Data are representative of two independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4385854&req=5

Figure 2: MiR-100 expression increases upon basal-like Breast Cancer Stem Cell (BrCSC) differentiationA, miR-100 expression in BrCSCs derived from human breast tumors evaluated by TaqMan RT-PCR. MiR-100 expression is reported as fold changes compared to P1. P1-P4: luminal; P5-P8: basal-like. B, miR-100 expression in basal-like BrCSCs (P5) before and after growth in differentiation condition, at the indicated times. Data are representative of two independent experiments.

Mentions: The level of miR-100 expression might be critical in maintaining stemness and in determining the transition from a stem to a differentiated status in cancer cells. When miR-100 expression was analyzed in a panel of CSCs isolated from basal-like and luminal breast cancer specimens (Supplementary Table 1), lower average levels of miR-100 were found in the CSCs derived from basal-like tumors (Fig. 2A). BrCSCs derived from patient 5 (P5), classified as basal-like subtype and expressing the lowest level of miR-100, were selected for further experiments. These cells displayed low levels also of the other two members of the miR-100 family, namely miR-99a and miR-99b (Supplementary Fig. 2A). The expression of the miRNAs in P5 BrCSCs was evaluated upon growth in conditions which favored differentiation. As shown in Fig. 2B and Supplementary Fig. 2B, the level of the miRNAs promptly increased upon differentiation.


By promoting cell differentiation, miR-100 sensitizes basal-like breast cancer stem cells to hormonal therapy.

Petrelli A, Carollo R, Cargnelutti M, Iovino F, Callari M, Cimino D, Todaro M, Mangiapane LR, Giammona A, Cordova A, Montemurro F, Taverna D, Daidone MG, Stassi G, Giordano S - Oncotarget (2015)

MiR-100 expression increases upon basal-like Breast Cancer Stem Cell (BrCSC) differentiationA, miR-100 expression in BrCSCs derived from human breast tumors evaluated by TaqMan RT-PCR. MiR-100 expression is reported as fold changes compared to P1. P1-P4: luminal; P5-P8: basal-like. B, miR-100 expression in basal-like BrCSCs (P5) before and after growth in differentiation condition, at the indicated times. Data are representative of two independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4385854&req=5

Figure 2: MiR-100 expression increases upon basal-like Breast Cancer Stem Cell (BrCSC) differentiationA, miR-100 expression in BrCSCs derived from human breast tumors evaluated by TaqMan RT-PCR. MiR-100 expression is reported as fold changes compared to P1. P1-P4: luminal; P5-P8: basal-like. B, miR-100 expression in basal-like BrCSCs (P5) before and after growth in differentiation condition, at the indicated times. Data are representative of two independent experiments.
Mentions: The level of miR-100 expression might be critical in maintaining stemness and in determining the transition from a stem to a differentiated status in cancer cells. When miR-100 expression was analyzed in a panel of CSCs isolated from basal-like and luminal breast cancer specimens (Supplementary Table 1), lower average levels of miR-100 were found in the CSCs derived from basal-like tumors (Fig. 2A). BrCSCs derived from patient 5 (P5), classified as basal-like subtype and expressing the lowest level of miR-100, were selected for further experiments. These cells displayed low levels also of the other two members of the miR-100 family, namely miR-99a and miR-99b (Supplementary Fig. 2A). The expression of the miRNAs in P5 BrCSCs was evaluated upon growth in conditions which favored differentiation. As shown in Fig. 2B and Supplementary Fig. 2B, the level of the miRNAs promptly increased upon differentiation.

Bottom Line: Moreover, miR-100 favors BrCSC differentiation, converting a basal like phenotype into luminal.It induces the expression of a functional estrogen receptor (ER) and renders basal-like BrCSCs responsive to hormonal therapy.Our findings indicate a new possible therapeutic strategy, which could make aggressive breast cancers responsive to standard treatments.

View Article: PubMed Central - PubMed

Affiliation: University of Torino School of Medicine, Candiolo Cancer Institute-FPO, IRCCS, Str. Provinciale, Candiolo, Torino, Italy.

ABSTRACT
Basal-like breast cancer is an aggressive tumor subtype with a poor response to conventional therapies. Tumor formation and relapse are sustained by a cell subset of Breast Cancer Stem Cells (BrCSCs). Here we show that miR-100 inhibits maintenance and expansion of BrCSCs in basal-like cancer through Polo-like kinase1 (Plk1) down-regulation. Moreover, miR-100 favors BrCSC differentiation, converting a basal like phenotype into luminal. It induces the expression of a functional estrogen receptor (ER) and renders basal-like BrCSCs responsive to hormonal therapy. The key role played by miR-100 in breast cancer free-survival is confirmed by the analysis of a cohort of patients' tumors, which shows that low expression of miR-100 is a negative prognostic factor and is associated with gene signatures of high grade undifferentiated tumors. Our findings indicate a new possible therapeutic strategy, which could make aggressive breast cancers responsive to standard treatments.

Show MeSH
Related in: MedlinePlus