Poster abstracts
Poster number 84 submitted by Fatimah Matalkah
A glance at the role of KHDRBS3 in the tumorigenesis of TNBC
Fatimah K Matalkah (Biochemistry/WVU), Bohye Jeong (Biochemistry/WVU), Peter Stoilov (Biochemistry/WVU)
Abstract:
TNBC has the worst prognosis among other breast cancer subtypes, and women diagnosed with the disease lack targeted treatments therapy. To identify possible molecular targets for treatment of TNBC, we analyzed the gene expression and alternative exon inclusion in more than 900 breast carcinoma and 120 normal breast tissue samples provided by the cancer genome atlas project (TCGA). We found that both the molecular basal like and the histological triple negative breast cancer (TNBC) subtypes display a distinct and very similar splicing profile. We also noticed high expression in the transcript level of the splicing factor KHDRBS3 in both subtypes. We examined the expression of KHDRBS3 in patient tumor samples and in a panel of breast cancer cell lines. We observed a higher protein level expression in the patient tumors and cell lines of TNBC relative to the ER/PR positive or normal mammary epithelial cells. To investigate, if the higher expression of KHRBS3 protein level would translate to an enhanced oncogenic property in the TNBC. We used two independent shRNA to stably knockdown the expression of KHDRBS3 in the cellular model of MDA-231-LN. Knocking down KHDRBS3 had no impact on cell proliferation or migration in vitro. To test if depletion of KHDRBS3 would have a different impact on TNBC progression and metastasis in vivo. MDA-231-LN expressing shKHDRBS3 were orthotopically transplanted into the mammary fat pad of female NSG mice. KHDRBS3 exhaustion had no significant outcome in the xenograft tumor growth rate. Neither it had a significant impact on the experimental or spontaneous metastasis to the lungs. While depletion of KHDRBS3 had no effect on the oncogenic properties of the selected cellular model, nevertheless we pursued to investigate the complete ablation of KHDRBS3 on spontaneous tumor formation of TNBC animal model. Indeed, we utilized the C3.1-Tag mouse model of triple negative breast cancer and back-crossed it to animals with either KHDRBS3 -/+, or KHDRBS3 -/- background. Surprisingly, complete ablation of KHDRBS3 from the mammary gland significantly hinder the formation of spontaneous mammary tumor. In conclusion, our data show that KHDRBS3 expression can probably be used as a molecular signature in TNBC.
Keywords: TNBC, KHDRBS3