乳腺癌是女性最常见的恶性肿瘤之一，据资料统计，发病率占全身各种恶性肿瘤的7-10%。它的发病常与遗传有关，以及40—60岁之间、绝经期前后的妇女发病率较高。
科学界已发现，女性体内细胞中如果缺乏STAT1蛋白质，会增加患乳腺癌的风险。近日，奥地利维也纳兽医大学在Breast Cancer Research杂志上论文称：该校研究人员发现了体内细胞缺乏STAT1蛋白质增加患乳腺癌几率的具体机理。
动物实验显示，实验鼠体内细胞中的STAT1蛋白质缺乏后，其癌细胞明显增多，同时其体内的免疫系统也被削弱，进而导致癌细胞增生更加迅速。
研究还发现，如果细胞中有足够的STAT1蛋白质，免疫细胞T细胞就能够识别癌细胞并杀死它们，从而增加乳腺癌患者的康复机会。(生物谷 Bioon.com)
doi:10.1186/bcr3100
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STAT1-deficient mice spontaneously develop estrogen receptor α-positive luminal mammary carcinomas
Szeman R Chan, William Vermi, Jingqin Luo, Laura Lucini, Charles Rickert, Amy M Fowler, Silvia Lonardi, Cora Arthur, Larry JT Young, David E Levy, Michael J Welch, Robert D Cardiff and Robert D Schreiber*
Introduction
Although breast cancers expressing estrogen receptor-alpha (ERalpha) and progesterone receptors (PR) are the most common form of mammary malignancy in humans, it has been difficult to develop a suitable mouse model showing similar steroid hormone responsiveness. STAT transcription factors play critical roles in mammary gland tumorigenesis, but the precise role of STAT1 remains unclear. Herein, we show that a subset of human breast cancers display reduced STAT1 expression and that mice lacking STAT1 surprisingly develop ERalpha+/PR+ mammary tumors.
Methods
We used a combination of approaches, including histological examination, gene targeted mice, gene expression analysis, tumor transplantaion, and immunophenotyping, to pursue this study.
Results
45% (37/83) of human ERalpha+ and 22% (17/78) of ERalpha- breast cancers display undetectable or low levels of STAT1 expression in neoplastic cells. In contrast, STAT1 expression is elevated in epithelial cells of normal breast tissues adjacent to the malignant lesions, suggesting that STAT1 is selectively downregulated in the tumor cells during tumor progression. Interestingly, the expression levels of STAT1 in the tumor-infiltrating stromal cells remain elevated, indicating that single-cell resolution analysis of STAT1 level in primary breast cancer biopsies is necessary for accurate assessment. Female mice lacking functional STAT1 spontaneously develop mammary adenocarcinomas that comprise >90% ERalpha+/PR+ tumor cells, and depend on estrogen for tumor engraftment and progression. Phenotypic markers analyses demonstrate that STAT1-/- mammary tumors arise from luminal epithelial cells, but not myoepithelial cells. In addition, the molecular signature of the STAT1-/- mammary tumors overlaps closely to that of human luminal breast cancers. Finally, introduction of wildtype STAT1, but not a STAT1 mutant lacking the critical Tyr701 residue, into STAT1-/- mammary tumor cells results in apoptosis, demonstrating that the tumor suppressor function of STAT1 is cell-autonomous and requires its transcriptional activity.
Conclusions
Our findings demonstrate that STAT1 suppresses mammary tumor formation and its expression is frequently lost during breast cancer progression. Spontaneous mammary tumors that develop in STAT1-/- mice closely recapitulate the progression, ovarian hormone responsiveness, and molecular characteristics of human luminal breast cancer, the most common subtype of human breast neoplasms, and thus represent a valuable platform for testing novel treatments and detection modalities.
