Oncogene-dependent expression of CD44 in Balb/c 3T3 derivatives: correlation with metastatic competence.
Oncogene-dependent expression of CD44 in Balb/c 3T3 derivatives: correlation with metastatic competence.
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Balb/c 3T3 衍生物中 CD44 的癌基因依赖性表达：与转移能力的相关性。
DOI：
10.1007/bf00157688
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发表时间：
1996
影响因子：
4
通讯作者：
Culp,LA
中科院分区：
文献类型：
--
作者：
Kogerman,P;Sy,MS;Culp,LA
在Balb/c 3T3细胞及其衍生物转染不同癌基因（转移性肿瘤模型）或人c- sic癌基因（非转移性模型）后，研究了CD44表达的癌基因依赖性调控和肿瘤相关性。使用Harvey或Kirsten癌基因的rastram子表达高水平的结合荧光透明质酸（HA）的细胞表面CD44蛋白。在亲代3T3细胞、kirsten转化细胞产生的ras -逆转体或c- sistrans子中，CD44的表达水平要低得多，这证实了治疗癌基因在这种上调中的重要性。为了确定内源性HA是否调节这些参数，透明质酸酶处理的透射子使更多的细胞表面CD44暴露于抗CD44抗体和增加荧光化HA结合；这在3T3或c- sistram子中没有发生。CD44的表达和它的ha结合功能在一组由转入子衍生的活体和肺转移性肿瘤细胞系中是保守的。在融合培养中，rastransforts还保留了下调CD44蛋白水平的能力，这是通过翻译或翻译后机制发生的（因为CD44 mRNA水平没有降低）。综上所述，这些结果表明，依赖于ras的CD44调控可能与肿瘤进展和体内转移相关，可能（尽管不是完全）支持CD44在转移进展中的重要性。
Oncogene-dependent regulation and tumor relatedness of CD44 expression were investigated in Balb/c 3T3 cells and their derivatives transformed with differentrasoncogenes (metastatic tumor model) or the human c-sisoncogene (non-metastatic model).Rastransformants using either the Harvey or Kirsten oncogenes expressed high levels of cell surface CD44 protein that bound fluoresceinated hyaluronan (HA). Much lower levels of CD44 were expressed in parental 3T3 cells,ras−revertants generated from Kirsten-transformed cells, or c-sistransformants, confirming the significance of therasoncogene in this upregulation. To determine whether endogenous HA regulates these parameters, hyaluronidase treatment ofrastransformants exposed more cell surface CD44 to anti-CD44 antibody and increased fluoresceinated HA binding; this did not occur with 3T3 or c-sistransformants. CD44 expression and its HA-binding function were conserved in a panel ofin vivoprimary and lung metastatic tumor cell lines derived fromrastransformants.Rastransformants also retained the ability to downregulate CD44 protein levels in confluent cultures which occurred through a translational or post-translational mechanism (as CD44 mRNA levels were not reduced). These results taken together demonstrate thatras-dependent regulation of CD44 may correlate with tumor progression and metastasisin vivo, possibly (although not exclusively) supporting CD44's importance in metastatic progression.