Limits...
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

Inhibition of HER2 elevates PAQR3 expression in SKBR3 cells(A, B) Effect of PAQR3 on HER2 expression. The mRNA levels of PAQR3 and HER2 were measured by quantitative RT-PCR in SKBR3 cells infected with lentivirus that had overexpression of PAQR3 or knockdown of PAQR3 by a PAQR3-specific shRNA. (C) Inhibition of HER2 increased PAQR3 expression. SKBR3 cells were treated with various concentrations of trastuzumab for 72 hours before analysis of PAQR3 mRNA level by quantitative RT-PCR. All the data are shown as mean ± SD and * for P < 0.05 and ** for P < 0.01 as compared to the control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4494943&req=5

Figure 6: Inhibition of HER2 elevates PAQR3 expression in SKBR3 cells(A, B) Effect of PAQR3 on HER2 expression. The mRNA levels of PAQR3 and HER2 were measured by quantitative RT-PCR in SKBR3 cells infected with lentivirus that had overexpression of PAQR3 or knockdown of PAQR3 by a PAQR3-specific shRNA. (C) Inhibition of HER2 increased PAQR3 expression. SKBR3 cells were treated with various concentrations of trastuzumab for 72 hours before analysis of PAQR3 mRNA level by quantitative RT-PCR. All the data are shown as mean ± SD and * for P < 0.05 and ** for P < 0.01 as compared to the control group.

Mentions: Since our clinical data indicate that PAQR3 expression level is inversely correlated with HER2 expression level, we next explored the regulation of HER2 by PAQR3 and vice versa. Interestingly, overexpression or knockdown of PAQR3 in HER2-positive SKBR3 cells could not alter the mRNA level of HER2 (Figure 6A and 6B). On the other hand, inhibition of HER2 by trastuzumab could dose-dependently increase PAQR3 expression in these cells (Figure 6C). Collectively, these data suggest that HER2 might regulate PAQR3 expression but PAQR3 has no effect on HER2 expression.


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)

Inhibition of HER2 elevates PAQR3 expression in SKBR3 cells(A, B) Effect of PAQR3 on HER2 expression. The mRNA levels of PAQR3 and HER2 were measured by quantitative RT-PCR in SKBR3 cells infected with lentivirus that had overexpression of PAQR3 or knockdown of PAQR3 by a PAQR3-specific shRNA. (C) Inhibition of HER2 increased PAQR3 expression. SKBR3 cells were treated with various concentrations of trastuzumab for 72 hours before analysis of PAQR3 mRNA level by quantitative RT-PCR. All the data are shown as mean ± SD and * for P < 0.05 and ** for P < 0.01 as compared to the control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Inhibition of HER2 elevates PAQR3 expression in SKBR3 cells(A, B) Effect of PAQR3 on HER2 expression. The mRNA levels of PAQR3 and HER2 were measured by quantitative RT-PCR in SKBR3 cells infected with lentivirus that had overexpression of PAQR3 or knockdown of PAQR3 by a PAQR3-specific shRNA. (C) Inhibition of HER2 increased PAQR3 expression. SKBR3 cells were treated with various concentrations of trastuzumab for 72 hours before analysis of PAQR3 mRNA level by quantitative RT-PCR. All the data are shown as mean ± SD and * for P < 0.05 and ** for P < 0.01 as compared to the control group.
Mentions: Since our clinical data indicate that PAQR3 expression level is inversely correlated with HER2 expression level, we next explored the regulation of HER2 by PAQR3 and vice versa. Interestingly, overexpression or knockdown of PAQR3 in HER2-positive SKBR3 cells could not alter the mRNA level of HER2 (Figure 6A and 6B). On the other hand, inhibition of HER2 by trastuzumab could dose-dependently increase PAQR3 expression in these cells (Figure 6C). Collectively, these data suggest that HER2 might regulate PAQR3 expression but PAQR3 has no effect on HER2 expression.

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