Porras Lucas, Gorse Faustine, Thiombane Ndeye Khady, Gaboury Louis, Mader Sylvie
Institute for Research in Immunology and Cancer, Faculty of Medicine, Université de Montréal, Montréal, QC H3C 3J7, Canada.
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Cancers (Basel). 2022 Nov 6;14(21):5453. doi: 10.3390/cancers14215453.
Estrogen receptor alpha (ERα) expression in ~2/3 breast tumors selects patients for hormonal therapies. Tumors negative for ERα but positive for the progesterone receptor (PR, encoded by ) have also been candidates for ER-targeting therapies, as PR expression may reflect undetected ER activity. Conversely, PR status in ER tumors predicts a worse therapeutic response. Our analysis of breast tumor transcriptome datasets, however, revealed that in tumors with lower expression, the clinical PR status does not correlate accurately with the expression of or of ER target genes, including itself. We identified carbonic anhydrase 12 () as an estrogen target gene better correlated with than , reflecting regulation by both ERα and the luminal factor and upstream regulator GATA3. Immunostaining supported strong positive correlations at the protein level with ERα and GATA3 in a cohort of 118 tumors. Most ERPR tumors expressed CAXII at levels similar to those of ERPR tumors, consistent with observations in tumor transcriptome datasets and with active estrogenic signaling in some ERPR breast cancer cell lines. The few ERPR tumors did not express CAXII or the other luminal markers FOXA1 and GATA3. Overall, CAXII is a luminal marker that can help interpret ER status in single ER/PR positive tumors.
约三分之二的乳腺肿瘤中雌激素受体α（ERα）的表达情况可用于筛选适合激素疗法的患者。雌激素受体α阴性但孕激素受体（PR，由 编码）阳性的肿瘤也一直是雌激素受体靶向治疗的候选对象，因为PR的表达可能反映了未被检测到的雌激素受体活性。相反，雌激素受体阳性肿瘤中的PR状态预示着较差的治疗反应。然而，我们对乳腺肿瘤转录组数据集的分析表明，在 表达水平较低的肿瘤中，临床PR状态与 或雌激素受体靶基因（包括 自身）的表达并无准确关联。我们将碳酸酐酶12（）鉴定为一种雌激素靶基因，它与 的相关性比 更好，这反映了其受雌激素受体α和管腔因子以及上游 调节因子GATA3的共同调控。免疫染色结果支持在118例肿瘤队列中，其蛋白水平与雌激素受体α和GATA3呈强正相关。大多数雌激素受体阳性孕激素受体阴性（ERPR）肿瘤中 的表达水平与雌激素受体阳性孕激素受体阳性（ERPR）肿瘤相似，这与肿瘤转录组数据集中的观察结果以及一些ERPR乳腺癌细胞系中的活跃雌激素信号传导一致。少数ERPR肿瘤不表达 或其他管腔标志物FOXA1和GATA3。总体而言， 是一种管腔标志物，可帮助解读单雌激素受体/孕激素受体阳性肿瘤中的雌激素受体状态。
