Accession Number : ADA545002


Title :   Identifying Breast Cancer Oncogenes


Descriptive Note : Annual summary rept. 1 Oct 2009-30 Sep 2010


Corporate Author : DANA-FARBER CANCER INST BOSTON MA


Personal Author(s) : Shrestha, Yashaswi


Full Text : http://www.dtic.mil/dtic/tr/fulltext/u2/a545002.pdf


Report Date : Oct 2010


Pagination or Media Count : 25


Abstract : Breast cancer is attributed to genetic alterations, the majority of which are yet to be characterized. Oncogenic alterations that give rise to breast tumors need to be identified in order to drive development of more efficient targeted or personalized cancer therapeutics and consequently, improve clinical outcomes. We aim to identify novel drivers of breast oncogenesis. We hypothesize that a kinase gain-of function screen in human mammary epithelial cells (HMEC) will reveal novel breast cancer oncogenes and provide potential targets for drug development. Our study is based on a transformation model that requires simultaneous activation of two RAS effector pathways: PI3K/AKT and MAPK, to transform human mammary epithelial cells. A pBabe-Puro-Myr-Flag kinase open reading frame (ORF) library was screened in immortalized human mammary epithelial cells (HMLE) expressing myr-AKT1 (HMLEA). Three kinases PTK6, PAK1 and CAMK4 promoted robust anchorage-independent growth in soft agar and are further being validated to understand their mechanism of action and relevance in human cancer. Here, we report that PTK6 behaves as a cooperating oncogene to enhance human mammary transformation. In collaboration with Joan Brugge's laboratory, we further determined that PTK6 activates IGF1R as well as RAS effector signaling to enhance anchorage-independent survival of mammary epithelial cells.


Descriptors :   *ONCOGENIC VIRUSES , *BREAST CANCER , THERAPY , DRUGS , TRANSFORMATIONS , MAMMARY GLANDS , NEOPLASMS , EPITHELIUM , CELLS(BIOLOGY)


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE