Shoker B S, Jarvis C, Davies M P, Iqbal M, Sibson D R, Sloane J P
Dept. of Pathology, Royal Liverpool University Hospital, Duncan Building, Prescot Street, Liverpool, L69 3GA.
Br J Cancer. 2001 Apr 20;84(8):1064-9. doi: 10.1054/bjoc.2001.1705.
Cyclin D1 is associated with cell cycle regulation and has more recently been shown to stimulate the transcriptional functions of the oestrogen receptor (ER). Furthermore, in normal breast there is a negative association between expression of ER and the proliferation marker Ki67 indicating that either ER positive cells are non-dividing or that the receptor is down-regulated as cells enter cycle. This important relationship breaks down in many ER-positive cancers and precancerous breast lesions where the receptor is often detected on proliferating cells. The aims of the present study were to determine the interplay between ER, Ki67 and cyclin D(1)in individual cells within the spectrum of human breast lesions ranging from normal to invasive carcinoma by using dual staining immunofluorescence. We found that in normal breast there was a strong positive association between ER and cyclin D(1)expression. In contrast there was a strong negative association between cyclin D(1)and Ki67 expression. Similar findings were seen for the other precancerous and cancerous breast lesions. Thus immunodetectable cyclin D(1)within individual cells does not appear to be associated with cell cycle progression in the benign or malignant breast but instead may have important interactions with ER.
细胞周期蛋白D1与细胞周期调控相关,最近研究表明它还能刺激雌激素受体(ER)的转录功能。此外,在正常乳腺组织中,ER表达与增殖标志物Ki67之间呈负相关,这表明要么ER阳性细胞不进行分裂,要么细胞进入细胞周期时该受体表达下调。在许多ER阳性癌症和癌前乳腺病变中,这种重要关系被打破,在这些病变中,增殖细胞上常常能检测到该受体。本研究的目的是通过双重免疫荧光染色,确定在从正常乳腺到浸润性癌的一系列人类乳腺病变的单个细胞中,ER、Ki67和细胞周期蛋白D1之间的相互作用。我们发现,在正常乳腺组织中,ER与细胞周期蛋白D1的表达之间存在强正相关。相反,细胞周期蛋白D1与Ki67的表达之间存在强负相关。在其他癌前和癌性乳腺病变中也观察到了类似的结果。因此,在单个细胞中可免疫检测到的细胞周期蛋白D1似乎与良性或恶性乳腺组织中的细胞周期进程无关,而是可能与ER存在重要的相互作用。