Howe C C, Kath R, Mancianti M L, Herlyn M, Mueller S, Cristofalo V
Wistar Institute, Philadelphia, Pennsylvania 19104.
Exp Cell Res. 1990 Jun;188(2):185-91. doi: 10.1016/0014-4827(90)90158-7.
A mouse SPARC cDNA clone was used to elucidate the expression of SPARC mRNA in normal diploid human cells as well as in tumor cells. Among 40 cell lines examined, 19 showed expression. The mRNA transcribed by the majority of the expressors are 2.1 kb with a trace amount of 3 kb. However, three cell types, undifferentiated basal keratinocytes, their differentiated derivatives, and breast adenocarcinoma cells, showed an expression pattern distinct from the typical one, having abundant 3-kb mRNA but no detectable 2.1-kb mRNA. The mRNA was translated and the product secreted. This expression pattern was not observed before in human cells and was not found in tumor cells of keratinocytes, squamous carcinoma cells, or many other adenocarcinoma cells. We showed by Northern hybridization that the SPARC-expressing melanocytic melanoma cell lines produced laminin, a component of extracellular matrix. Other cell types expressing the SPARC mRNA were also reported to synthesize extracellular matrix components. Thus, our results indicate an association between SPARC gene expression and production of extracellular matrix. However, the opposite is not true since non-SPARC-producers may or may not produce extracellular matrix. For example, A431 cell line, which does not express SPARC mRNA, is known to produce extracellular matrix components while the normal diploid melanocytes and undifferentiated embryonal carcinoma cells, which do not express SPARC mRNA, do not produce extracellular matrix component.
利用小鼠SPARC cDNA克隆来阐明SPARC mRNA在正常二倍体人类细胞以及肿瘤细胞中的表达情况。在所检测的40种细胞系中,有19种呈现表达。大多数表达细胞系转录的mRNA为2.1 kb,有少量3 kb的。然而,三种细胞类型,即未分化的基底角质形成细胞、其分化衍生物以及乳腺腺癌细胞,呈现出与典型模式不同的表达模式,具有丰富的3 kb mRNA但检测不到2.1 kb mRNA。该mRNA被翻译且产物被分泌。这种表达模式在人类细胞中此前未被观察到,在角质形成细胞肿瘤细胞、鳞状癌细胞或许多其他腺癌细胞中也未发现。我们通过Northern杂交表明,表达SPARC的黑素细胞性黑色素瘤细胞系产生层粘连蛋白,这是细胞外基质的一种成分。据报道,其他表达SPARC mRNA的细胞类型也合成细胞外基质成分。因此,我们的结果表明SPARC基因表达与细胞外基质产生之间存在关联。然而,反之则不成立,因为不产生SPARC的细胞可能产生也可能不产生细胞外基质。例如,不表达SPARC mRNA的A431细胞系已知能产生细胞外基质成分,而不表达SPARC mRNA的正常二倍体黑素细胞和未分化的胚胎癌细胞则不产生细胞外基质成分。