Murphy L C, Hilsenbeck S G, Dotzlaw H, Fuqua S A
Department of Biochemistry, University of Manitoba, Winnipeg, Manitoba, R3E 0W3, Canada.
Clin Cancer Res. 1995 Feb;1(2):155-9.
To gain insight into the possible biological role of variant estrogen receptor (ER) expression in human breast cancer, we have undertaken a study to determine if the expression of the clone 4 variant ER mRNA was associated with markers of either reduced endocrine sensitivity [i.e., progesterone receptor (PgR) negativity] or a poor prognosis (node positivity, large tumor size, and high percentage S-phase fraction). mRNA levels of clone 4 variant ER and wild-type (WT) ER were assayed by RNase protection assay in 106 breast cancer specimens. The tumors comprised two major groups: "good" prognosis and "poor" prognosis based on several conventional biological prognostic features. Each group was divided into three subgroups (ER+/PgR+, ER+/PgR-, and ER-/PgR-). WT and clone 4 variant ER mRNAs were undetected in ER-/PgR- tumors. We determined that clone 4 variant ER mRNA levels varied proportionately with WT mRNA levels, and regression analysis was used to determine if the amount of clone 4 variant ER mRNA relative to WT was associated with prognosis or PgR content. Significantly higher levels of clone 4 variant ER mRNA relative to WT were found in tumors with markers of poor prognosis compared to those with markers of good prognosis (P = 0.0004). Significantly higher levels of clone 4 variant ER mRNA relative to WT were found in PgR- tumors compared to PgR+ tumors (P = 0.011). Such data are consistent with an association of clone 4 variant ER mRNA expression with progression of human breast cancer from hormone dependence to independence.
为深入了解变异雌激素受体（ER）表达在人类乳腺癌中可能的生物学作用，我们开展了一项研究，以确定克隆4变异ER mRNA的表达是否与内分泌敏感性降低的标志物（即孕激素受体（PgR）阴性）或预后不良（淋巴结阳性、肿瘤体积大、S期分数百分比高）相关。通过核糖核酸酶保护试验检测了106例乳腺癌标本中克隆4变异ER和野生型（WT）ER的mRNA水平。根据几种传统的生物学预后特征，这些肿瘤分为两个主要组：“预后良好”组和“预后不良”组。每组又分为三个亚组（ER+/PgR+、ER+/PgR-和ER-/PgR-）。在ER-/PgR-肿瘤中未检测到WT和克隆4变异ER mRNA。我们确定克隆4变异ER mRNA水平与WT mRNA水平成比例变化，并使用回归分析来确定克隆4变异ER mRNA相对于WT的量是否与预后或PgR含量相关。与预后良好标志物的肿瘤相比，预后不良标志物的肿瘤中克隆4变异ER mRNA相对于WT的水平显著更高（P = 0.0004）。与PgR+肿瘤相比，PgR-肿瘤中克隆4变异ER mRNA相对于WT的水平显著更高（P = 0.011）。这些数据与克隆4变异ER mRNA表达与人类乳腺癌从激素依赖向激素非依赖进展的关联一致。
