1. Functional Analysis of Human mRNAs in Bronchioloalveolar Carcinoma
Matthew Thompson, Hawken School, 2013
Callie Merry, Maya Ratnam, Ahmad Khalil Ph.D.
Case Western Reserve University
Cancer of the lung and bronchus is a global epidemic and is expected to account for over 25% of
cancer related deaths in 2013. Additionally, lung cancer has been the leading cause of cancerous
death since before 1995. Non-small-cell lung cancer (NSCLC) is a particularly aggressive lung
cancer with less than a 50% survival rate even when identified in its early stages. A non-invasive
form of NSCLC, known as Bronchioloalveolar Carcinoma (BAC), accounts for 20% of NSCLC
cases; however, environmental triggers can convert benign tumors into invasive ones. We
hypothesized that the invasiveness of BAC is caused by up-regulation of the mRNA, Poly-C
Binding Protein 3 (PCBP3), which has been shown to be up-regulated between the cancerous
and invasive stages of the BAC model. We performed siRNA knockdown of PCBP3 on the
human invasive lung cancer cell line A549. A double basement-membrane invasion assay
revealed that PCBP3 knockdown conferred ~1.5-2 fold increase in invasiveness (standard
error=.3). Moreover, Western Blot analysis revealed that PCBP3 knockdown caused a decrease
in E-Cadherin protein levels, a gene frequently cited as a tumor suppressor in breast, prostate,
and lung cancers, among others. Our preliminary findings suggest that PCBP3 may have a
downstream effect on mediation of E-Cadherin levels, and thus PCBP3 upregulation may be a
response to BAC’s invasive progression. Although further work needs to be done to validate
these findings in an independent cell line, this preliminary data represents a promising step
toward isolating the genetic factors in the BAC model.