乳腺癌是女性最常見(jiàn)的惡性腫瘤之一,，據(jù)資料統(tǒng)計(jì),，發(fā)病率占全身各種惡性腫瘤的7-10%,。它的發(fā)病常與遺傳有關(guān),，以及40—60歲之間,、絕經(jīng)期前后的婦女發(fā)病率較高。
科學(xué)界已發(fā)現(xiàn),，女性體內(nèi)細(xì)胞中如果缺乏STAT1蛋白質(zhì),，會(huì)增加患乳腺癌的風(fēng)險(xiǎn)。近日,，奧地利維也納獸醫(yī)大學(xué)在Breast Cancer Research雜志上論文稱：該校研究人員發(fā)現(xiàn)了體內(nèi)細(xì)胞缺乏STAT1蛋白質(zhì)增加患乳腺癌幾率的具體機(jī)理,。
動(dòng)物實(shí)驗(yàn)顯示，實(shí)驗(yàn)鼠體內(nèi)細(xì)胞中的STAT1蛋白質(zhì)缺乏后,，其癌細(xì)胞明顯增多,，同時(shí)其體內(nèi)的免疫系統(tǒng)也被削弱，進(jìn)而導(dǎo)致癌細(xì)胞增生更加迅速,。
研究還發(fā)現(xiàn),，如果細(xì)胞中有足夠的STAT1蛋白質(zhì)，免疫細(xì)胞T細(xì)胞就能夠識(shí)別癌細(xì)胞并殺死它們,，從而增加乳腺癌患者的康復(fù)機(jī)會(huì),。(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.
