Abstract：
:Screening of the entire let-7 family of microRNAs (miRNA) by in situ hybridization identified let-7g as the only member, the diminished expression of which was significantly associated with lymph node metastasis and poor survival in breast cancer patients. Abrogation of let-7g expression in otherwise nonmetastatic mammary carcinoma cells elicited rapid metastasis from the orthotopic location, through preferential targets, Grb2-associated binding protein 2 (GAB2) and fibronectin 1 (FN1), and consequent activation of p44/42 mitogen-activated protein kinase (MAPK) and specific matrix metalloproteinases. Treatment with estrogen or epidermal growth factor specifically reduced the expression of mature let-7g through activation of p44/42 MAPK and subsequently stimulated expression of GAB2 and FN1, which, in turn, promoted tumor invasion. We thus identify let-7g as a unique member of the let-7 miRNA family that can serve as a prognostic biomarker in breast cancer and also propose a paradigm used by specific signaling molecules via let-7g to cooperatively promote breast cancer invasion and metastasis. Thus, let-7 family members neither possess equivalent clinicopathologic correlation nor function in breast cancer.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Qian P,Zuo Z,Wu Z,Meng X,Li G,Wu Z,Zhang W,Tan S,Pandey V,Yao Y,Wang P,Zhao L,Wang J,Wu Q,Song E,Lobie PE,Yin Z,Zhu Tdoi
10.1158/0008-5472.CAN-11-1322subject
Has Abstractpub_date
2011-10-15 00:00:00pages
6463-74issue
20eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-11-1322journal_volume
71pub_type
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