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BRCA1 regulates PIG3-mediated apoptosis in a p53-dependent manner.

Zhang W, Luo J, Chen F, Yang F, Song W, Zhu A, Guan X - Oncotarget (2015)

Bottom Line: Moreover, we reveal that overexpression of BRCA1 significantly increased expression of PIG3 in cells with intact p53, whereas no increase in PIG3 was observed in p53- MDA-MB-157 cells and p53-depleted HCT116p53-/- cells.Meanwhile, ectopic expression of BRCA1 could not lead to an increase expression level of prohibitin (PHB), which we have previously identified to induce PIG3-mediated apoptosis.Finally, ChIP analysis revealed that PHB can bind to the PIG3 promoter and activate PIG3 transcription independent of p53, although p53 presence did enhance this process.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China.

ABSTRACT
BRCA1 plays a key role in the regulation of p53-dependent target gene transcription activation. Meanwhile, the p53 inducible gene 3 (PIG3) is a downstream target of p53 and is involved in p53-initiated apoptosis. However, little is known about whether BRCA1 can regulate PIG3-mediated apoptosis. Using a tissue microarray containing 149 breast cancer patient samples, we found that BRCA1 and PIG3 expression status were significantly positively correlated (r = 0.678, P < 0.001) and identified a significant positive correlation between high expression of BRCA1 and/or PIG3 and overall survival (OS). Moreover, we reveal that overexpression of BRCA1 significantly increased expression of PIG3 in cells with intact p53, whereas no increase in PIG3 was observed in p53- MDA-MB-157 cells and p53-depleted HCT116p53-/- cells. Meanwhile, ectopic expression of BRCA1 could not lead to an increase expression level of prohibitin (PHB), which we have previously identified to induce PIG3-mediated apoptosis. Finally, ChIP analysis revealed that PHB can bind to the PIG3 promoter and activate PIG3 transcription independent of p53, although p53 presence did enhance this process. Taken together, our findings suggest that BRCA1 regulates PIG3-mediated apoptosis in a p53-dependent manner, and that PIG3 expression is associated with a better OS in breast cancer patients.

No MeSH data available.


Related in: MedlinePlus

PIG3 and BRCA1 are associated with OS in breast cancer patients(A) High magnification (200×) regions shown immunohistochemical analysis of PIG3 and BRCA1 high or low expression breast cancer patient tissues. (B) High PIG3 and/or BRCA1 expression was associated with better OS (all P < 0.05).
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Figure 1: PIG3 and BRCA1 are associated with OS in breast cancer patients(A) High magnification (200×) regions shown immunohistochemical analysis of PIG3 and BRCA1 high or low expression breast cancer patient tissues. (B) High PIG3 and/or BRCA1 expression was associated with better OS (all P < 0.05).

Mentions: To evaluate the putative association between PIG3 and BRCA1 with overall survival (OS) in human breast cancer, we performed immunohistochemical (IHC) staining of these proteins in malignant tumor samples from 149 patients using a tissue microarray (Figure 1A). High PIG3 expression was associated with better OS (Figure 1B, 102.08 vs. 81.10 months; P = 0.004) and high BRCA1 expression was also associated with better OS (102.40 vs. 81.15 months; P = 0.004). Moreover, OS was improved when the expressions of PIG3 and BRCA1 were both high (Figure 1B, 100.32 vs. 72.39 months; P < 0.001). Demographic, pathological, and clinical variables were collected and the correlation of these with PIG3 and BRCA1 expression was determined (Table 1). Of the 149 tumor tissues, 95 cases (63.8%) and 54 cases (36.2%) expressed PIG3 at high and low levels, respectively, while 97 cases (65.1%) and 52 cases (34.9%) expressed BRCA1 at high and low levels, respectively. Age, tumor size, and lymph nodal status were not significantly associated with PIG3 or BRCA1 expression (Table 1). We then determined whether a correlation between PIG3 and BRCA1 exists by using tumor microarrays (Table 2). A significant positive correlation between PIG3 and BRCA1 expression was identified using the breast cancer tissue-array (r = 0.678, P < 0.001). Taken together, these data suggest that PIG3 expression was positively associated with BRCA1 expression, and that high PIG3 and/or BRCA1 expression was associated with better OS in human breast cancer patients.


BRCA1 regulates PIG3-mediated apoptosis in a p53-dependent manner.

Zhang W, Luo J, Chen F, Yang F, Song W, Zhu A, Guan X - Oncotarget (2015)

PIG3 and BRCA1 are associated with OS in breast cancer patients(A) High magnification (200×) regions shown immunohistochemical analysis of PIG3 and BRCA1 high or low expression breast cancer patient tissues. (B) High PIG3 and/or BRCA1 expression was associated with better OS (all P < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4480703&req=5

Figure 1: PIG3 and BRCA1 are associated with OS in breast cancer patients(A) High magnification (200×) regions shown immunohistochemical analysis of PIG3 and BRCA1 high or low expression breast cancer patient tissues. (B) High PIG3 and/or BRCA1 expression was associated with better OS (all P < 0.05).
Mentions: To evaluate the putative association between PIG3 and BRCA1 with overall survival (OS) in human breast cancer, we performed immunohistochemical (IHC) staining of these proteins in malignant tumor samples from 149 patients using a tissue microarray (Figure 1A). High PIG3 expression was associated with better OS (Figure 1B, 102.08 vs. 81.10 months; P = 0.004) and high BRCA1 expression was also associated with better OS (102.40 vs. 81.15 months; P = 0.004). Moreover, OS was improved when the expressions of PIG3 and BRCA1 were both high (Figure 1B, 100.32 vs. 72.39 months; P < 0.001). Demographic, pathological, and clinical variables were collected and the correlation of these with PIG3 and BRCA1 expression was determined (Table 1). Of the 149 tumor tissues, 95 cases (63.8%) and 54 cases (36.2%) expressed PIG3 at high and low levels, respectively, while 97 cases (65.1%) and 52 cases (34.9%) expressed BRCA1 at high and low levels, respectively. Age, tumor size, and lymph nodal status were not significantly associated with PIG3 or BRCA1 expression (Table 1). We then determined whether a correlation between PIG3 and BRCA1 exists by using tumor microarrays (Table 2). A significant positive correlation between PIG3 and BRCA1 expression was identified using the breast cancer tissue-array (r = 0.678, P < 0.001). Taken together, these data suggest that PIG3 expression was positively associated with BRCA1 expression, and that high PIG3 and/or BRCA1 expression was associated with better OS in human breast cancer patients.

Bottom Line: Moreover, we reveal that overexpression of BRCA1 significantly increased expression of PIG3 in cells with intact p53, whereas no increase in PIG3 was observed in p53- MDA-MB-157 cells and p53-depleted HCT116p53-/- cells.Meanwhile, ectopic expression of BRCA1 could not lead to an increase expression level of prohibitin (PHB), which we have previously identified to induce PIG3-mediated apoptosis.Finally, ChIP analysis revealed that PHB can bind to the PIG3 promoter and activate PIG3 transcription independent of p53, although p53 presence did enhance this process.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China.

ABSTRACT
BRCA1 plays a key role in the regulation of p53-dependent target gene transcription activation. Meanwhile, the p53 inducible gene 3 (PIG3) is a downstream target of p53 and is involved in p53-initiated apoptosis. However, little is known about whether BRCA1 can regulate PIG3-mediated apoptosis. Using a tissue microarray containing 149 breast cancer patient samples, we found that BRCA1 and PIG3 expression status were significantly positively correlated (r = 0.678, P < 0.001) and identified a significant positive correlation between high expression of BRCA1 and/or PIG3 and overall survival (OS). Moreover, we reveal that overexpression of BRCA1 significantly increased expression of PIG3 in cells with intact p53, whereas no increase in PIG3 was observed in p53- MDA-MB-157 cells and p53-depleted HCT116p53-/- cells. Meanwhile, ectopic expression of BRCA1 could not lead to an increase expression level of prohibitin (PHB), which we have previously identified to induce PIG3-mediated apoptosis. Finally, ChIP analysis revealed that PHB can bind to the PIG3 promoter and activate PIG3 transcription independent of p53, although p53 presence did enhance this process. Taken together, our findings suggest that BRCA1 regulates PIG3-mediated apoptosis in a p53-dependent manner, and that PIG3 expression is associated with a better OS in breast cancer patients.

No MeSH data available.


Related in: MedlinePlus