Kalinina T S, Kononchuk V V, Sidorov S V, Gulyaeva L F
Institute of Molecular Biology and Biophysics - Subdivision of Federal Research Center of Fundamental and Translational Medicine, Novosibirsk, Russia.
Novosibirsk State University, Novosibirsk, Russia; Municipal Clinical Hospital No.1, Novosibirsk, Russia.
Biomed Khim. 2020 Jan;66(1):89-94. doi: 10.18097/PBMC20206601089.
Breast cancer (BC) is the most common cancer among women. It is known that the prolactin receptor (PRLR) may play a role in breast carcinogenesis, but the available data are often contradictory. To get a more complete picture of the relationship between the receptor and mammary gland carcinogenesis, we examined the association between changes in PRLR expression level and tumor subtype (and its main characteristics). To do this, using real-time PCR, we evaluated the level of PRLR mRNA in BC tissue samples and untransformed adjoining tissue samples (89 pairs). Since the androgen receptor (AR) has begun to be seen as a prognostic marker in breast cancer, we also evaluated the association between mRNA levels of AR and PRLR. We found a significant increase in PRLR expression in luminal subtypes; the highest level of PRLR mRNA was detected in luminal A subtype. In HER2-positive ER-, PR-negative BC, the PRLR mRNA level decreases in tumor tissues compared with untransformed tissues. High PRLR expression is also associated with smaller tumor size in luminal B HER2-negative subtype. In ER-, PR-negative tumors, PRLR expression is associated with AR expression: PRLR mRNA level is increased when AR mRNA level is reduced by more than 8 times in triple-negative tumors; in contrast, in HER2-positive subtype it decreases more significantly when AR expression is reduced by more than 3 times. A tendency towards an increase in PRLR expression with an increase in the AR mRNA level was also discovered in luminal subtypes. The level of PRLR expression depends on the age of patients. In luminal A, PRLR expression is higher in patients under 65 years. In contrast, in luminal B HER2-negative and triple-negative BC, reduced PRLR expression was observed in patients under the age of 40 years and under the age of 50 years, respectively. In this group of patients under the age of 40 years with luminal B HER2-negative BC, ER expression was also reduced (0-4 score according to the IHC assay). Thus, PRLR probably plays a different role in the development and progression of BC: in luminal A and luminal B HER2-positive subtypes PRLR may act as an oncogen, and in luminal B HER2-negative and ER-, PR-negative subtypes can play a tumor suppressor role.
乳腺癌(BC)是女性中最常见的癌症。已知催乳素受体(PRLR)可能在乳腺癌发生过程中起作用,但现有数据往往相互矛盾。为了更全面地了解该受体与乳腺肿瘤发生之间的关系,我们研究了PRLR表达水平变化与肿瘤亚型(及其主要特征)之间的关联。为此,我们使用实时PCR评估了89对乳腺癌组织样本和未转化的相邻组织样本中PRLR mRNA的水平。由于雄激素受体(AR)已开始被视为乳腺癌的一种预后标志物,我们还评估了AR和PRLR的mRNA水平之间的关联。我们发现管腔亚型中PRLR表达显著增加;在管腔A型中检测到最高水平的PRLR mRNA。在HER2阳性、雌激素受体(ER)和孕激素受体(PR)阴性的乳腺癌中,肿瘤组织中PRLR mRNA水平与未转化组织相比降低。在管腔B型HER2阴性亚型中,高PRLR表达也与较小的肿瘤大小相关。在ER和PR阴性肿瘤中,PRLR表达与AR表达相关:在三阴性肿瘤中,当AR mRNA水平降低超过8倍时,PRLR mRNA水平升高;相反,在HER2阳性亚型中,当AR表达降低超过3倍时,PRLR表达下降更显著。在管腔亚型中还发现随着AR mRNA水平升高PRLR表达有增加的趋势。PRLR表达水平取决于患者年龄。在管腔A型中,65岁以下患者的PRLR表达较高。相反,在管腔B型HER2阴性和三阴性乳腺癌中,分别在40岁以下和50岁以下患者中观察到PRLR表达降低。在这组40岁以下的管腔B型HER2阴性乳腺癌患者中,ER表达也降低(根据免疫组化分析评分为0 - 4分)。因此,PRLR可能在乳腺癌的发生和发展中发挥不同作用:在管腔A型和管腔B型HER2阳性亚型中,PRLR可能作为一种癌基因起作用,而在管腔B型HER2阴性和ER、PR阴性亚型中可发挥肿瘤抑制作用。