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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.


Related in: MedlinePlus

mRNA expression of LPA receptor 1-3 in breast tissues. a To determine whether the samples expressed LPA receptors, quantitative real-time PCR was performed by LPA1, LPA2, and LPA3 primers. The relative gene expression was calculated against GAPDH. b The relative LPA1 mRNA expression in normal breast epithelium, mammary with benign disease, and malignant tissues. c The relative LPA2 mRNA expression in normal breast epithelium, mammary with benign disease, and malignant tissues. d The relative LPA3 mRNA expression in normal breast epithelium, mammary with benign disease, and malignant tissues. ***P < 0.001
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Fig1: mRNA expression of LPA receptor 1-3 in breast tissues. a To determine whether the samples expressed LPA receptors, quantitative real-time PCR was performed by LPA1, LPA2, and LPA3 primers. The relative gene expression was calculated against GAPDH. b The relative LPA1 mRNA expression in normal breast epithelium, mammary with benign disease, and malignant tissues. c The relative LPA2 mRNA expression in normal breast epithelium, mammary with benign disease, and malignant tissues. d The relative LPA3 mRNA expression in normal breast epithelium, mammary with benign disease, and malignant tissues. ***P < 0.001

Mentions: We evaluated mRNA expression of LPA1–3 in normal, benign, and malignant breast epithelium; mRNA levels were quantified against GAPDH. As shown in Fig. 1a, breast tissues predominantly expressed LPA1 and LPA2, whereas LPA3 expression was weakly but detectable in all specimens. Similar levels of LPA1 mRNA were detected in normal, benign, and carcinoma tissues (0.11 ± 0.058 vs. 0.13 ± 0.044 vs. 0.13 ± 0.034, P = 0.789; Fig. 1b). However, LPA2 mRNA levels in breast cancers were significantly higher than that in normal tissue (0.17 ± 0.070 vs. 0.13 ± 0.072, P = 0.0002; Fig. 1c). Although low levels of LPA3 were observed in all breast tissues, the cancer tissues exhibited a greater expression of LPA3 than did normal (0.05 ± 0.023 vs. 0.02 ± 0.002, P < 0.001) or benign-disease tissues (0.05 ± 0.023 vs. 0.03 ± 0.002, P < 0.001) (Fig. 1d). Notably, LPA3 expression was also greater in benign-disease tissue than in normal tissue (0.03 ± 0.002 vs. 0.02 ± 0.002, P = 0.009; Fig. 1d).Fig. 1


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)

mRNA expression of LPA receptor 1-3 in breast tissues. a To determine whether the samples expressed LPA receptors, quantitative real-time PCR was performed by LPA1, LPA2, and LPA3 primers. The relative gene expression was calculated against GAPDH. b The relative LPA1 mRNA expression in normal breast epithelium, mammary with benign disease, and malignant tissues. c The relative LPA2 mRNA expression in normal breast epithelium, mammary with benign disease, and malignant tissues. d The relative LPA3 mRNA expression in normal breast epithelium, mammary with benign disease, and malignant tissues. ***P < 0.001
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Fig1: mRNA expression of LPA receptor 1-3 in breast tissues. a To determine whether the samples expressed LPA receptors, quantitative real-time PCR was performed by LPA1, LPA2, and LPA3 primers. The relative gene expression was calculated against GAPDH. b The relative LPA1 mRNA expression in normal breast epithelium, mammary with benign disease, and malignant tissues. c The relative LPA2 mRNA expression in normal breast epithelium, mammary with benign disease, and malignant tissues. d The relative LPA3 mRNA expression in normal breast epithelium, mammary with benign disease, and malignant tissues. ***P < 0.001
Mentions: We evaluated mRNA expression of LPA1–3 in normal, benign, and malignant breast epithelium; mRNA levels were quantified against GAPDH. As shown in Fig. 1a, breast tissues predominantly expressed LPA1 and LPA2, whereas LPA3 expression was weakly but detectable in all specimens. Similar levels of LPA1 mRNA were detected in normal, benign, and carcinoma tissues (0.11 ± 0.058 vs. 0.13 ± 0.044 vs. 0.13 ± 0.034, P = 0.789; Fig. 1b). However, LPA2 mRNA levels in breast cancers were significantly higher than that in normal tissue (0.17 ± 0.070 vs. 0.13 ± 0.072, P = 0.0002; Fig. 1c). Although low levels of LPA3 were observed in all breast tissues, the cancer tissues exhibited a greater expression of LPA3 than did normal (0.05 ± 0.023 vs. 0.02 ± 0.002, P < 0.001) or benign-disease tissues (0.05 ± 0.023 vs. 0.03 ± 0.002, P < 0.001) (Fig. 1d). Notably, LPA3 expression was also greater in benign-disease tissue than in normal tissue (0.03 ± 0.002 vs. 0.02 ± 0.002, P = 0.009; Fig. 1d).Fig. 1

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