Taja-Chayeb Lucia, Chavez-Blanco Alma, Martínez-Tlahuel Jorge, González-Fierro Aurora, Candelaria Myrna, Chanona-Vilchis Jose, Robles Elizabeth, Dueñas-Gonzalez Alfonso
Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología/Instituto de Investigaciones Biomédicas, UNAM, Mexico.
Cancer Cell Int. 2006 Oct 2;6:22. doi: 10.1186/1475-2867-6-22.
Despite significant achievements in the treatment of cervical cancer, it is still a deadly disease; hence newer therapeutical modalities are needed. Preliminary investigations suggest that platelet-derived growth factor (PDGF) might have a role in the development of cervical cancer, therefore it is important to determine whether this growth factor pathway is functional and its targeting with imatinib mesylate leads to growth inhibition of cervical cancer cells.
PDGF receptors (PDGFR) and their ligands are frequently expressed in cervical cancer and the majority exhibited a combination of family members co-expression. A number of intronic and exonic variations but no known mutations in the coding sequence of the PDGFRalpha gene were found in cancer cell lines and primary tumors. Growth assays demonstrated that PDGFBB induces growth stimulation that can be blocked by imatinib and that this tyrosine kinase inhibitor on its own inhibits cell growth. These effects were associated with the phosphorylation status of the receptor.
The PDGFR system may have a role in the pathogenesis of cervical cancer as their members are frequently expressed in this tumor and cervical cancer lines are growth inhibited by the PDGFR antagonist imatinib.
尽管宫颈癌治疗取得了显著成就,但它仍是一种致命疾病;因此需要更新的治疗方法。初步研究表明,血小板衍生生长因子(PDGF)可能在宫颈癌的发展中起作用,因此确定该生长因子途径是否发挥作用以及用甲磺酸伊马替尼靶向该途径是否会导致宫颈癌细胞生长抑制非常重要。
PDGF受体(PDGFR)及其配体在宫颈癌中经常表达,且大多数呈现家庭成员共表达的组合。在癌细胞系和原发性肿瘤中发现了许多内含子和外显子变异,但在PDGFRα基因的编码序列中未发现已知突变。生长试验表明,PDGFBB诱导的生长刺激可被伊马替尼阻断,且这种酪氨酸激酶抑制剂自身可抑制细胞生长。这些效应与受体的磷酸化状态有关。
PDGFR系统可能在宫颈癌的发病机制中起作用,因为其成员在该肿瘤中经常表达,且宫颈癌系被PDGFR拮抗剂伊马替尼抑制生长。