Accession Number : ADA601036


Title :   Transdifferentiation between Luminal- and Basal-Type Cancer Cells


Descriptive Note : Final rept. 15 Mar 2011-14 Sep 2013


Corporate Author : MASSACHUSETTS UNIV MEDICAL SCHOOL WORCESTER


Personal Author(s) : Du, Cheng


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a601036.pdf


Report Date : Dec 2013


Pagination or Media Count : 44


Abstract : Breast cancer is a highly diverse group of cancers and consists of at least 5 different subgroups. Furthermore, patients with Intra-tumor heterogeneity due to the presence of cancer cells with variable phenotypes such as different degrees of basal-like and luminal features increase the complexity of treatment. The aim of this project is to better understand the mechanisms that regulate breast cancer cell plasticity and origins of breast cancer heterogeneity. Our focus is the function of protein kinase D1 (PKD1), which is a serine/threonine kinase. We previously showed that PKD1 can repress epithelial to mesenchymal transition (EMT) by inhibitory phosphorylation of transcription factor Snail, a master switch of EMT. Supported by this award, we have performed experiments on molecular, cellular, mice xenografts and transgenic levels and conclude that PKD1 is a context-dependent tumorigenesis and metastasis repressor or enhance. Specifically, PKD1 is a metastasis repressor in luminal type breast cancer and loss of PKD1 in luminal type cells converts them into basal-like cells; and PKD1 is an enhancer of tumorigenesis in basal-like breast cancer. Based on current available data, conditional knockout PKD1 in mouse mammary tissue does not disrupt mammary development and does not induce tumorigenesis.


Descriptors :   *BREAST CANCER , AMINO ACIDS , EPITHELIUM , GENETIC DISEASES , GROWTH(PHYSIOLOGY) , METASTASIS , PHOSPHORUS TRANSFERASES , PHOSPHORYLATION , SURGICAL TRANSPLANTATION


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE