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PAQR3 expression is downregulated in human breast cancers and correlated with HER2 expression.

Li Z, Ling ZQ, Guo W, Lu XX, Pan Y, Wang Z, Chen Y - Oncotarget (2015)

Bottom Line: Knockdown of PAQR3 in MDA-MD-231 cells elevated cell proliferation and migration.PAQR3 is able to modulate the proliferation and migration of breast cancer cells.Our data indicate that PAQR3 functions as a tumor suppressor in the development of human breast cancers.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.

ABSTRACT
PAQR3 is a newly discovered tumor suppressor and its functional role in breast cancer has not been well characterized. We report here that PAQR3 is associated with the progression and survival of human patients with breast cancer, as well as cell proliferation and migration of human breast cancer cells. PAQR3 mRNA level was robustly downregulated in human breast cancer samples compared with their corresponding para-cancerous histological normal tissues (n = 82, P < 0.0001). The mRNA level of PAQR3 was negatively correlated with HER2 expression (P < 0.0001) and disease-free survival of the patients (P < 0.0001). PAQR3 overexpression inhibited cell proliferation, colony formation and migration of breast cancer cells including MCF7, SKBR3, MDA-MD-231, MDA-MD-468 and MDA-MD-453 cells. Knockdown of PAQR3 in MDA-MD-231 cells elevated cell proliferation and migration. Inhibition of HER2 by trastuzumab increased PAQR3 expression in SKBR3 cells. In conclusion, PAQR3 expression is frequently downregulated in human breast cancers inversely correlated with HER2 expression. PAQR3 is able to modulate the proliferation and migration of breast cancer cells. Our data indicate that PAQR3 functions as a tumor suppressor in the development of human breast cancers.

No MeSH data available.


Related in: MedlinePlus

Correlation of PAQR3 expression level with survival of breast cancer patientsKaplan-Meier curves of disease-free survival (DFS, shown in A) and overall survival (OS, shown in B) in post-surgery patients with breast cancers according to the expression level of PAQR3.
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Figure 2: Correlation of PAQR3 expression level with survival of breast cancer patientsKaplan-Meier curves of disease-free survival (DFS, shown in A) and overall survival (OS, shown in B) in post-surgery patients with breast cancers according to the expression level of PAQR3.

Mentions: We next investigated the association of PAQR3 expression level with the survival of the patients. Both disease-free survival (DFS) and overall survival (OS) were determined. DFS was defined as the time from surgery to first recurrence and OS was the time from surgery to death. We found that the average duration of DFS in patients with PAQR3 downregulation in the tumors was significantly shorter than those with normal to high expression of PAQR3 in the tumors (Figure 2 and Table 2). The average DFS in patients with low expression of PAQR3 was 64.1 months vs 95.9 months in patients with normal to high expression of PAQR3 (Table 2, P < 0.0001). However, the average OS was only slightly different between the patients with low expression of PAQR3 and those with normal to high expression of PAQR3 (Table 2, P = 0.081). This was likely due to the fact that we only analyzed the patient survival for about 5 years and most patients were still alive due to effective therapy. In addition, we observed that a few other previously characterized clinical parameters were associated with patient survival (Table 2), such as lymph node metastasis (P = 0.021) and TNM stage (P = 0.043). Collectively, these data indicate that the expression level of PAQR3 might serve as an independent marker to predict the survival of the breast cancer patients.


PAQR3 expression is downregulated in human breast cancers and correlated with HER2 expression.

Li Z, Ling ZQ, Guo W, Lu XX, Pan Y, Wang Z, Chen Y - Oncotarget (2015)

Correlation of PAQR3 expression level with survival of breast cancer patientsKaplan-Meier curves of disease-free survival (DFS, shown in A) and overall survival (OS, shown in B) in post-surgery patients with breast cancers according to the expression level of PAQR3.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494943&req=5

Figure 2: Correlation of PAQR3 expression level with survival of breast cancer patientsKaplan-Meier curves of disease-free survival (DFS, shown in A) and overall survival (OS, shown in B) in post-surgery patients with breast cancers according to the expression level of PAQR3.
Mentions: We next investigated the association of PAQR3 expression level with the survival of the patients. Both disease-free survival (DFS) and overall survival (OS) were determined. DFS was defined as the time from surgery to first recurrence and OS was the time from surgery to death. We found that the average duration of DFS in patients with PAQR3 downregulation in the tumors was significantly shorter than those with normal to high expression of PAQR3 in the tumors (Figure 2 and Table 2). The average DFS in patients with low expression of PAQR3 was 64.1 months vs 95.9 months in patients with normal to high expression of PAQR3 (Table 2, P < 0.0001). However, the average OS was only slightly different between the patients with low expression of PAQR3 and those with normal to high expression of PAQR3 (Table 2, P = 0.081). This was likely due to the fact that we only analyzed the patient survival for about 5 years and most patients were still alive due to effective therapy. In addition, we observed that a few other previously characterized clinical parameters were associated with patient survival (Table 2), such as lymph node metastasis (P = 0.021) and TNM stage (P = 0.043). Collectively, these data indicate that the expression level of PAQR3 might serve as an independent marker to predict the survival of the breast cancer patients.

Bottom Line: Knockdown of PAQR3 in MDA-MD-231 cells elevated cell proliferation and migration.PAQR3 is able to modulate the proliferation and migration of breast cancer cells.Our data indicate that PAQR3 functions as a tumor suppressor in the development of human breast cancers.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.

ABSTRACT
PAQR3 is a newly discovered tumor suppressor and its functional role in breast cancer has not been well characterized. We report here that PAQR3 is associated with the progression and survival of human patients with breast cancer, as well as cell proliferation and migration of human breast cancer cells. PAQR3 mRNA level was robustly downregulated in human breast cancer samples compared with their corresponding para-cancerous histological normal tissues (n = 82, P < 0.0001). The mRNA level of PAQR3 was negatively correlated with HER2 expression (P < 0.0001) and disease-free survival of the patients (P < 0.0001). PAQR3 overexpression inhibited cell proliferation, colony formation and migration of breast cancer cells including MCF7, SKBR3, MDA-MD-231, MDA-MD-468 and MDA-MD-453 cells. Knockdown of PAQR3 in MDA-MD-231 cells elevated cell proliferation and migration. Inhibition of HER2 by trastuzumab increased PAQR3 expression in SKBR3 cells. In conclusion, PAQR3 expression is frequently downregulated in human breast cancers inversely correlated with HER2 expression. PAQR3 is able to modulate the proliferation and migration of breast cancer cells. Our data indicate that PAQR3 functions as a tumor suppressor in the development of human breast cancers.

No MeSH data available.


Related in: MedlinePlus