Smith G H, Mehrel T, Roop D R
Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Cell Growth Differ. 1990 Apr;1(4):161-70.
Two keratins whose expression has been associated with proliferation (K14) and hyperproliferation (K6) in mouse epithelia were detected in normal, preneoplastic, and neoplastic mouse mammary tissues. K6 and K14 keratins were independently expressed in distinct epithelial cell populations in developing mammary anlage. K6 was confined to a small number of mammary epithelial cells associated with the growing end buds and among the proximal luminal epithelium, whereas K14 expression appeared in basally located fusiform cells that correspond to the location of mammary myoepithelial cells. This pattern was maintained in mature glands and through full functional differentiation with the exception that K6-positive cells were only rarely detectable. During lobuloalveolar growth in early pregnancy, K6 and K6/K14 coexpressing cells were observed among the luminal and suprabasal cells in the expanding lobular epithelium. This K6/K14 coexpressing epithelial subset persisted throughout pregnancy, lactation, and involution, albeit in much smaller numbers than observed in early pregnancy. Two patterns of K6 and K14 expression in preneoplastic and neoplastic lesions of mouse mammary glands were induced by various carcinogenic stimuli. In one, increased numbers of K6- or K14-positive cells were present in distinct cellular populations; in the other, coexpression of K6/K14 was found in a large subpopulation of both preneoplastic and neoplastic mammary epithelium. These observations suggest that expression of K6 and K14 keratins in the mouse mammary gland is associated with growth and expansion of specific mammary epithelial cell populations, and as such these keratins may be useful probes with which to identify mammary epithelium-specific primordial cells. In agreement with this possibility, K6/K14 expression was demonstrated within a distinct subset of morphologically distinct luminal mammary epithelial cells that have been reported to possess kinetic properties in vitro consistent with those expected of latent mammogenic stem cells.
在正常、癌前和肿瘤性小鼠乳腺组织中检测到两种角蛋白，其表达与小鼠上皮中的增殖（K14）和过度增殖（K6）相关。K6和K14角蛋白在发育中的乳腺原基的不同上皮细胞群体中独立表达。K6局限于与生长中的终末芽相关的少数乳腺上皮细胞以及近端管腔上皮中，而K14表达出现在基部的梭形细胞中，这些细胞对应于乳腺肌上皮细胞的位置。这种模式在成熟腺体中以及整个功能完全分化过程中得以维持，只是K6阳性细胞很少能被检测到。在妊娠早期的小叶腺泡生长过程中，在扩张的小叶上皮的管腔和基底上层细胞中观察到了K6以及K6/K14共表达的细胞。这种K6/K14共表达的上皮亚群在整个妊娠、哺乳和退化过程中持续存在，尽管数量比妊娠早期观察到的要少得多。小鼠乳腺的癌前和肿瘤性病变中K6和K14的表达模式受各种致癌刺激诱导产生两种情况。一种情况是，在不同细胞群体中K6或K14阳性细胞数量增加；另一种情况是，在癌前和肿瘤性乳腺上皮的大量亚群中发现了K6/K14的共表达。这些观察结果表明，小鼠乳腺中K6和K14角蛋白的表达与特定乳腺上皮细胞群体的生长和扩张相关，因此这些角蛋白可能是识别乳腺上皮特异性原始细胞的有用探针。与此可能性一致的是，在形态学上不同的管腔乳腺上皮细胞的一个独特亚群中证实了K6/K14的表达，据报道这些细胞在体外具有与潜在生乳干细胞预期相符的动力学特性。
