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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

Expression of PAQR3 is reduced in human breast cancer samples and inversely correlated with HER2 expressionThe relative level of PAQR3 mRNA in human breast cancer tissues in comparison with PCHNT specimen from 82 breast cancer patients is shown in (A) PAQR3 mRNA level was determined by quantitative RT-PCR and adjusted for GAPDH. The relative ratio of PAQR3 mRNA in the cancer samples vs PCHNT samples is shown in (B). The tumor/PCHNT ratio < 0.5 is considered as low expression. The correlation of PAQR3 mRNA level with HER2 expression is shown in (C). IHC was used to determine the protein expression level of HER2. The IHC score of HER2 is plotted with the mRNA level of PAQR3. Note that PAQR3 expression level is inversely correlated with HER2 expression level.
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Figure 1: Expression of PAQR3 is reduced in human breast cancer samples and inversely correlated with HER2 expressionThe relative level of PAQR3 mRNA in human breast cancer tissues in comparison with PCHNT specimen from 82 breast cancer patients is shown in (A) PAQR3 mRNA level was determined by quantitative RT-PCR and adjusted for GAPDH. The relative ratio of PAQR3 mRNA in the cancer samples vs PCHNT samples is shown in (B). The tumor/PCHNT ratio < 0.5 is considered as low expression. The correlation of PAQR3 mRNA level with HER2 expression is shown in (C). IHC was used to determine the protein expression level of HER2. The IHC score of HER2 is plotted with the mRNA level of PAQR3. Note that PAQR3 expression level is inversely correlated with HER2 expression level.

Mentions: To investigate the potential role of PAQR3 as a suppressor in human breast cancers, we characterized the expression status of PAQR3 transcript in 82 patients with primary breast cancer. The mRNA level of PAQR3 was determined in both the primary breast cancer samples together with their corresponding para-cancerous histological normal tissue (PCHNT). Intriguingly, we found that PAQR3 mRNA level was robustly reduced in most of the cancer samples compared to PCHNT. Using the standard of over two-fold change, PAQR3 mRNA was significantly lower in 58 tumors (70.7%, P < 0.0001) than the paired PCHNT samples (Figure 1A and 1B, Table 1). The mRNA level of PAQR3 was also associated with a few clinical characteristics of the patients (Table 1). The expression status of PAQR3 in the breast cancer samples was strongly correlated with the differentiation of the tumor (P < 0.0001), with low expression of PAQR3 associating with poor differentiation of the tumor. In addition, PAQR3 expression level was slightly associated with TNM stage (P = 0.044), with lower PAQR3 mRNA level associating with higher TNM stage.


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)

Expression of PAQR3 is reduced in human breast cancer samples and inversely correlated with HER2 expressionThe relative level of PAQR3 mRNA in human breast cancer tissues in comparison with PCHNT specimen from 82 breast cancer patients is shown in (A) PAQR3 mRNA level was determined by quantitative RT-PCR and adjusted for GAPDH. The relative ratio of PAQR3 mRNA in the cancer samples vs PCHNT samples is shown in (B). The tumor/PCHNT ratio < 0.5 is considered as low expression. The correlation of PAQR3 mRNA level with HER2 expression is shown in (C). IHC was used to determine the protein expression level of HER2. The IHC score of HER2 is plotted with the mRNA level of PAQR3. Note that PAQR3 expression level is inversely correlated with HER2 expression level.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Expression of PAQR3 is reduced in human breast cancer samples and inversely correlated with HER2 expressionThe relative level of PAQR3 mRNA in human breast cancer tissues in comparison with PCHNT specimen from 82 breast cancer patients is shown in (A) PAQR3 mRNA level was determined by quantitative RT-PCR and adjusted for GAPDH. The relative ratio of PAQR3 mRNA in the cancer samples vs PCHNT samples is shown in (B). The tumor/PCHNT ratio < 0.5 is considered as low expression. The correlation of PAQR3 mRNA level with HER2 expression is shown in (C). IHC was used to determine the protein expression level of HER2. The IHC score of HER2 is plotted with the mRNA level of PAQR3. Note that PAQR3 expression level is inversely correlated with HER2 expression level.
Mentions: To investigate the potential role of PAQR3 as a suppressor in human breast cancers, we characterized the expression status of PAQR3 transcript in 82 patients with primary breast cancer. The mRNA level of PAQR3 was determined in both the primary breast cancer samples together with their corresponding para-cancerous histological normal tissue (PCHNT). Intriguingly, we found that PAQR3 mRNA level was robustly reduced in most of the cancer samples compared to PCHNT. Using the standard of over two-fold change, PAQR3 mRNA was significantly lower in 58 tumors (70.7%, P < 0.0001) than the paired PCHNT samples (Figure 1A and 1B, Table 1). The mRNA level of PAQR3 was also associated with a few clinical characteristics of the patients (Table 1). The expression status of PAQR3 in the breast cancer samples was strongly correlated with the differentiation of the tumor (P < 0.0001), with low expression of PAQR3 associating with poor differentiation of the tumor. In addition, PAQR3 expression level was slightly associated with TNM stage (P = 0.044), with lower PAQR3 mRNA level associating with higher TNM stage.

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