Kitayama Joji, Shida Dai, Sako Akihiro, Ishikawa Makoto, Hama Kotaro, Aoki Junken, Arai Hiroyuki, Nagawa Hirokazu
Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan.
Breast Cancer Res. 2004;6(6):R640-6. doi: 10.1186/bcr935. Epub 2004 Sep 22.
Lysophosphatidic acid (LPA) is a bioactive phospholipid with diverse effects on various cells. It interacts with at least three G-protein-coupled transmembrane receptors, namely LPA1, LPA2 and LPA3, whose expression in various tumours has not been fully characterized. In the present study we characterized the expression profile of LPA receptors in human breast cancer tissue and assessed the possible roles of each receptor.
The relative expression levels of each receptor's mRNA against beta-actin mRNA was examined in surgically resected invasive ductal carcinomas and normal gland tissue using real-time RT-PCR. LPA2 expression was also examined immunohistochemically using a rat anti-LPA2 monoclonal antibody.
In 25 cases normal and cancer tissue contained LPA1 mRNA at similar levels, whereas the expression level of LPA2 mRNA was significantly increased in cancer tissue as compared with its normal counterpart (3479.0 +/- 426.6 versus 1287.3 +/- 466.8; P < 0.05). LPA3 was weakly expressed in both cancer and normal gland tissue. In 48 (57%) out of 84 cases, enhanced expression of LPA2 protein was confirmed in carcinoma cells as compared with normal mammary epithelium by immunohistochemistry. Over-expression of LPA2 was detected in 17 (45%) out of 38 premenopausal women, as compared with 31 (67%) out of 46 postmenopausal women, and the difference was statistically significant (P < 0.05).
These findings suggest that upregulation of LPA2 may play a role in carcinogenesis, particularly in postmenopausal breast cancer.
溶血磷脂酸（LPA）是一种对多种细胞具有多种作用的生物活性磷脂。它与至少三种G蛋白偶联跨膜受体相互作用，即LPA1、LPA2和LPA3，它们在各种肿瘤中的表达尚未完全明确。在本研究中，我们对人乳腺癌组织中LPA受体的表达谱进行了表征，并评估了每种受体可能的作用。
使用实时逆转录聚合酶链反应（RT-PCR）检测手术切除的浸润性导管癌和正常腺体组织中各受体mRNA相对于β-肌动蛋白mRNA的相对表达水平。还使用大鼠抗LPA2单克隆抗体通过免疫组织化学检测LPA2表达。
在25例中，正常组织和癌组织中LPA1 mRNA水平相似，而癌组织中LPA2 mRNA的表达水平与其正常对应物相比显著增加（3479.0±426.6对1287.3±466.8；P<0.05）。LPA3在癌组织和正常腺体组织中均弱表达。通过免疫组织化学证实，84例中有48例（57%）癌细胞中LPA2蛋白的表达与正常乳腺上皮相比增强。在38例绝经前女性中有17例（45%）检测到LPA2过表达，而在46例绝经后女性中有31例（67%），差异具有统计学意义（P<0.05）。
这些发现表明LPA2的上调可能在致癌过程中起作用，特别是在绝经后乳腺癌中。
