Porter R M, Lunny D P, Ogden P H, Morley S M, McLean W H, Evans A, Harrison D L, Rugg E L, Lane E B
CRC Cell Structure Research Group, University of Dundee, United Kingdom.
Lab Invest. 2000 Nov;80(11):1701-10. doi: 10.1038/labinvest.3780180.
Keratins are intermediate filament proteins whose expression in epithelial tissues is closely linked to their differentiated state. The greatest complexity of this expression is seen in the epidermis and associated structures. The critical basal (proliferative) cell layer expresses the major keratin pair, K5 and K14, but it also expresses an additional type I keratin, K15, about which far less is known. We have compared the expression of K15 with K14 in normal, pathological, and tissue culture contexts; distinct differences in their expression patterns have been observed that imply different regulation and function for these two genes. K15 appears to be preferentially expressed in stable or slowly turning over basal cells. In steady-state epidermis, K15 is present in higher amounts in basal cells of thin skin but in lower amounts in the rapidly turning over thick plantar skin. Although remaining high in basal cell carcinomas (noninvasive) it is suppressed in squamous cell carcinomas (which frequently metastasize). Wounding-stimulated epidermis loses K15 expression, whereas K14 is unchanged. In cultured keratinocytes, K15 levels are suppressed until the culture stratifies, whereas K14 is constitutively expressed throughout. Therefore, unlike K14, which appears to be a fundamental component of all keratinocytes, K15 expression appears to be more tightly coupled to a mature basal keratinocyte phenotype.
角蛋白是中间丝蛋白,其在上皮组织中的表达与它们的分化状态密切相关。这种表达的最大复杂性见于表皮及相关结构。关键的基底(增殖性)细胞层表达主要的角蛋白对,即K5和K14,但它也表达另一种I型角蛋白K15,目前对其了解较少。我们已经在正常、病理和组织培养环境中比较了K15和K14的表达;观察到它们表达模式的明显差异,这意味着这两个基因有不同的调控和功能。K15似乎优先在稳定或更新缓慢的基底细胞中表达。在稳态表皮中,K15在薄皮肤的基底细胞中含量较高,但在更新迅速的厚足底皮肤中含量较低。虽然在基底细胞癌(非侵袭性)中仍保持高水平,但在鳞状细胞癌(常发生转移)中受到抑制。伤口刺激的表皮会失去K15表达,而K14则保持不变。在培养的角质形成细胞中,K15水平在培养分层之前受到抑制,而K14在整个培养过程中持续表达。因此,与似乎是所有角质形成细胞基本成分的K14不同,K15的表达似乎与成熟的基底角质形成细胞表型更紧密相关。