Investigating differences between tamoxifen resistant and sensitive breast cancer cells with flow cytometry.
Investigating differences between tamoxifen resistant and sensitive breast cancer cells with flow cytometry.
复制标题
DOI：
10.1002/cyto.a.24306
复制
发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Houston KD
中科院分区：
文献类型：
--
作者：
Bitton A;Zheng Y;Houston JP;Houston KD
他莫昔芬的活性代谢产物4-羟基他莫昔芬在乳腺癌细胞中起抗雌激素作用，从而抑制增殖。虽然他莫昔芬继续成功地用于治疗雌激素依赖性乳腺癌，但大多数接受治疗的患者会随着时间的推移产生耐药性。他莫昔芬抵抗的两种常见生物标志物是胰岛素样生长因子1受体（IGF-1 R）表达减少和表皮生长因子受体（EGFR）表达增加。在以前的工作中，我们已经表明，这些受体促进化疗耐药性，并具有独特的调节功能，可测量耐药细胞系相比，非耐药。因此，我们假设这些受体和新鉴定的生物标志物整合素β1可用于在对他莫昔芬治疗敏感的细胞群中寻找耐药乳腺癌细胞的存在。我们通过设计一种简单的细胞标记方法来测试这一点，以通过细胞计数测量耐药细胞与敏感细胞的受体表达差异。我们的结果表明，当观察IGF-1 R以及整合素β1的表达时，分离是可能的。有趣的是，我们发现，尽管EGFR在耐药细胞中上调，但当用细胞术测量时，他莫昔芬耐药细胞和敏感细胞之间的EGFR表达没有可检测到的差异。我们的长期目标是利用分选来通过受体表达水平分离他莫昔芬抗性细胞亚群。分离存在于药物敏感细胞群体中的罕见耐药细胞将为为什么会发生化学耐药性提供新的见解。
The active metabolite of tamoxifen, 4‐hydroxytamoxifen, functions as an anti‐estrogen in breast cancer cells and thus inhibits proliferation. While tamoxifen continues to be successfully used to treat estrogen‐dependent breast cancer, most patients receiving treatment will develop chemoresistance over time. Two commonly reported biomarkers of tamoxifen resistance are decreased expression of insulin‐like growth factor 1 receptor (IGF‐1R) and increased expression of epidermal growth factor receptor (EGFR). In prior work we have shown that these receptors facilitate chemoresistance and have unique regulatory functions measurable in resistant cell lines compared with nonresistant. Thus, we hypothesized that these receptors and a newly identified biomarker, integrin β1, may be used to search for the presence of resistant breast cancer cells within a population of cells that are sensitive to tamoxifen therapy. We tested this by designing a straightforward cell‐labeling approach to measure differences in the receptor expression of resistant vs. sensitive cells cytometrically. Our results show that separation is possible when observing the expression of IGF‐1R as well as integrin β1. Interestingly, we found no detectable difference in EGFR expression between tamoxifen resistant and ‐sensitive cells when measured with cytometry despite the fact that EGFR is upregulated in resistant cells. Our long‐term goal is to utilize sorting to isolate tamoxifen resistant subpopulations of cells by receptor expression level. Isolating rare resistant cells that reside within a population of drug‐sensitive cells will offer new insights into why chemoresistance occurs.
登录
查看更多内容
影响因子：
3.5
作者：
Zheng, Yan;Houston, Kevin D.
通讯作者：
Houston, Kevin D.
影响因子：
7.5
作者：
Wang YN;Hung MC
通讯作者：
Hung MC
影响因子：
5.6
作者：
Quirke VM
通讯作者：
Quirke VM
影响因子：
254.7
作者：
DeSantis, Carol E.;Ma, Jiemin;Siegel, Rebecca L.
通讯作者：
Siegel, Rebecca L.
影响因子：
78.5
作者：
Desgrosellier, Jay S.;Cheresh, David A.
通讯作者：
Cheresh, David A.