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Aberrant expression and potential therapeutic target of lysophosphatidic acid receptor 3 in triple-negative breast cancers.

Sun K, Cai H, Duan X, Yang Y, Li M, Qu J, Zhang X, Wang J - Clin. Exp. Med. (2014)

Bottom Line: Carcinomas expressed higher levels of LPA2 and LPA3 mRNAs (0.17 ± 0.070 and 0.05 ± 0.023, respectively) than did normal breast tissue (0.13 ± 0.072 and 0.02 ± 0.002, respectively).The LPA3 overexpression was associated with lymph node metastases, and absence of estrogen receptor, progesterone receptors, and human epidermal growth factor receptor 2 expression.In conclusion, our data indicated that the expression of LPA receptor 3 was increased in human TNBCs and is associated with tumor metastatic ability, and this implies that LPA3 is a potential therapeutic target for the treatment of TNBCs.

View Article: PubMed Central - PubMed

Affiliation: The Second Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi, China.

ABSTRACT
Triple receptor-negative breast cancers (TNBCs) generally have poor prognoses because of the loss of therapeutic targets. As lysophosphatidic acid (LPA) receptor signaling has been shown to affect breast cancer initiation and progression, we try to evaluate the potential roles of LPA receptors in TNBCs. We examined mRNA and protein expressions of LPA receptors 1-3, using quantitative real-time PCR and immunohistochemical analyses in normal (n = 37), benign disease (n = 55), and breast cancer tissues (n = 82). Carcinomas expressed higher levels of LPA2 and LPA3 mRNAs (0.17 ± 0.070 and 0.05 ± 0.023, respectively) than did normal breast tissue (0.13 ± 0.072 and 0.02 ± 0.002, respectively). Enhanced immunohistochemical staining for LPA2 and LPA3 protein was also consistently observed in carcinomas. The LPA3 overexpression was associated with lymph node metastases, and absence of estrogen receptor, progesterone receptors, and human epidermal growth factor receptor 2 expression. TNBC tissues and cell lines showed the highest LPA3 expression compared with luminal-type A and B breast cancers. Suppression of LPA3 by shRNA did not influence cell growth in breast cancer cells. However, the migration and invasion of TNBC cells were significantly inhibited by LPA3-shRNA or inhibitor, which had no or less effect on normal and non-TNBC breast cells. In conclusion, our data indicated that the expression of LPA receptor 3 was increased in human TNBCs and is associated with tumor metastatic ability, and this implies that LPA3 is a potential therapeutic target for the treatment of TNBCs.

No MeSH data available.


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Protein levels of LPA receptor 1-3 in different breast tissues. a Immunostains for LPA receptor 1-3 in normal, benign disease and malignant breast tissue. b–d Quantification of immunostains for LPA receptor 1-3 by IOD analysis. *P < 0.05; ***P < 0.001
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Fig2: Protein levels of LPA receptor 1-3 in different breast tissues. a Immunostains for LPA receptor 1-3 in normal, benign disease and malignant breast tissue. b–d Quantification of immunostains for LPA receptor 1-3 by IOD analysis. *P < 0.05; ***P < 0.001

Mentions: We also immunohistochemically evaluated expression of LPA receptor proteins in the same specimens (Fig. 2a). LPA1–3 was detectable in the cell membrane and cytoplasm in most specimens (113/119 of LPA1, 116/119 of LPA2, and 110/119 of LPA3). As with the mRNA expression, enhanced staining for LPA2 and LPA3 protein was clearly detected in carcinomas in comparison with normal epithelium or benign-disease tissues (Fig. 2c, d), whereas LPA1 expression did not differ significantly between different groups (Fig. 2b). Protein immunoreactivity significant correlated with relative mRNA expression (r = 0.592, P < 0.001).Fig. 2


Aberrant expression and potential therapeutic target of lysophosphatidic acid receptor 3 in triple-negative breast cancers.

Sun K, Cai H, Duan X, Yang Y, Li M, Qu J, Zhang X, Wang J - Clin. Exp. Med. (2014)

Protein levels of LPA receptor 1-3 in different breast tissues. a Immunostains for LPA receptor 1-3 in normal, benign disease and malignant breast tissue. b–d Quantification of immunostains for LPA receptor 1-3 by IOD analysis. *P < 0.05; ***P < 0.001
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4522273&req=5

Fig2: Protein levels of LPA receptor 1-3 in different breast tissues. a Immunostains for LPA receptor 1-3 in normal, benign disease and malignant breast tissue. b–d Quantification of immunostains for LPA receptor 1-3 by IOD analysis. *P < 0.05; ***P < 0.001
Mentions: We also immunohistochemically evaluated expression of LPA receptor proteins in the same specimens (Fig. 2a). LPA1–3 was detectable in the cell membrane and cytoplasm in most specimens (113/119 of LPA1, 116/119 of LPA2, and 110/119 of LPA3). As with the mRNA expression, enhanced staining for LPA2 and LPA3 protein was clearly detected in carcinomas in comparison with normal epithelium or benign-disease tissues (Fig. 2c, d), whereas LPA1 expression did not differ significantly between different groups (Fig. 2b). Protein immunoreactivity significant correlated with relative mRNA expression (r = 0.592, P < 0.001).Fig. 2

Bottom Line: Carcinomas expressed higher levels of LPA2 and LPA3 mRNAs (0.17 ± 0.070 and 0.05 ± 0.023, respectively) than did normal breast tissue (0.13 ± 0.072 and 0.02 ± 0.002, respectively).The LPA3 overexpression was associated with lymph node metastases, and absence of estrogen receptor, progesterone receptors, and human epidermal growth factor receptor 2 expression.In conclusion, our data indicated that the expression of LPA receptor 3 was increased in human TNBCs and is associated with tumor metastatic ability, and this implies that LPA3 is a potential therapeutic target for the treatment of TNBCs.

View Article: PubMed Central - PubMed

Affiliation: The Second Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi, China.

ABSTRACT
Triple receptor-negative breast cancers (TNBCs) generally have poor prognoses because of the loss of therapeutic targets. As lysophosphatidic acid (LPA) receptor signaling has been shown to affect breast cancer initiation and progression, we try to evaluate the potential roles of LPA receptors in TNBCs. We examined mRNA and protein expressions of LPA receptors 1-3, using quantitative real-time PCR and immunohistochemical analyses in normal (n = 37), benign disease (n = 55), and breast cancer tissues (n = 82). Carcinomas expressed higher levels of LPA2 and LPA3 mRNAs (0.17 ± 0.070 and 0.05 ± 0.023, respectively) than did normal breast tissue (0.13 ± 0.072 and 0.02 ± 0.002, respectively). Enhanced immunohistochemical staining for LPA2 and LPA3 protein was also consistently observed in carcinomas. The LPA3 overexpression was associated with lymph node metastases, and absence of estrogen receptor, progesterone receptors, and human epidermal growth factor receptor 2 expression. TNBC tissues and cell lines showed the highest LPA3 expression compared with luminal-type A and B breast cancers. Suppression of LPA3 by shRNA did not influence cell growth in breast cancer cells. However, the migration and invasion of TNBC cells were significantly inhibited by LPA3-shRNA or inhibitor, which had no or less effect on normal and non-TNBC breast cells. In conclusion, our data indicated that the expression of LPA receptor 3 was increased in human TNBCs and is associated with tumor metastatic ability, and this implies that LPA3 is a potential therapeutic target for the treatment of TNBCs.

No MeSH data available.


Related in: MedlinePlus