Department of Pathology, Tianjin Union Medical Center, Tianjin, China.
Nankai University School of Medicine, Nankai University, Tianjin, China.
Cancer Sci. 2018 Jun;109(6):1825-1833. doi: 10.1111/cas.13620. Epub 2018 May 23.
The initiation of spontaneous breast cancer (SBC) in Tientsin Albino 2 (TA2) mice is related to mouse mammary tumor virus (MMTV) infection, and MMTV amplification is hormonally regulated. To explore the insertion site of MMTVLTR in TA2 mouse genome, reverse PCR and nested PCR were used to amplify the unknown sequence on both sides of the MMTV-LTRSAG gene in SBC and normal breast tissue of TA2 mice. Furthermore, the clinicopathological significance of the insertion site was evaluated in 43 samples of normal breast tissue, 46 samples of breast cystic hyperplasia, 54 samples of ductal carcinoma in situ, 142 samples of primary breast cancer and 47 samples of lymph node metastatic breast cancer by RNA in situ hybridization. We confirmed that the insertion site of the MMTV-LTRSAG gene was located between Igκv2-112 and Igκv14-111 in chromosome 6 of TA2 mouse. IGκC was localized in the stromal cells of TA2 mouse with SBC and in human breast cancer tissues. Tumor cells were negative for IGκC in RNA in situ hybridization. The positive staining index of IGκC in stromal cells was the highest in lymph node metastatic breast cancer, followed by primary breast cancer, ductal carcinoma in situ, and breast cystic hyperplasia. Furthermore, the positive staining index of IGκC was related to the expression of ER, PR, HER2 and Ki-67. Our findings showed that stromal IGκC expression was associated with the initiation of SBC in TA2 mice. IGκC may be a high-risk factor for the initiation and progression of human breast cancer.
自发性乳腺癌（SBC）在天津白化 2 号（TA2）小鼠中的发生与鼠乳腺肿瘤病毒（MMTV）感染有关，而 MMTV 的扩增受激素调节。为了探索 MMTVLTR 在 TA2 小鼠基因组中的插入位点，我们使用反转录 PCR 和嵌套 PCR 扩增了 SBC 和 TA2 小鼠正常乳腺组织中 MMTV-LTRSAG 基因两侧的未知序列。此外，通过 RNA 原位杂交技术，我们评估了该插入位点在 43 例正常乳腺组织、46 例乳腺囊性增生、54 例导管原位癌、142 例原发性乳腺癌和 47 例淋巴结转移性乳腺癌样本中的临床病理意义。我们证实，MMTV-LTRSAG 基因的插入位点位于 TA2 小鼠 6 号染色体上的 Igκv2-112 和 Igκv14-111 之间。IGκC 定位于具有 SBC 的 TA2 小鼠的间质细胞和人类乳腺癌组织中。在 RNA 原位杂交中，肿瘤细胞 IGκC 染色为阴性。在间质细胞中，IGκC 的阳性染色指数在淋巴结转移性乳腺癌中最高，其次是原发性乳腺癌、导管原位癌和乳腺囊性增生。此外，IGκC 的阳性染色指数与 ER、PR、HER2 和 Ki-67 的表达有关。我们的研究结果表明，间质 IGκC 的表达与 TA2 小鼠 SBC 的发生有关。IGκC 可能是人类乳腺癌发生和进展的高危因素。
