Accession Number : ADA464009


Title :   Role of Notch Signaling in Human Breast Cancer Pathogenesis


Descriptive Note : Annual summary 30 Jun 2003-29 Oct 2006


Corporate Author : INDIAN INST OF SCIENCE BANGALORE (INDIA)


Personal Author(s) : Rangarajan, Annapoorni


Full Text : http://www.dtic.mil/dtic/tr/fulltext/u2/a464009.pdf


Report Date : Nov 2006


Pagination or Media Count : 9


Abstract : Notch proteins are activated upon binding to ligands of the Delta/Serrate family. In previous experiments I had found that activated allele of Notch 1 cooperates with low levels of oncogenic Ras expressing HMLE cells(termed HMLER). Further investigations revealed that Notch-IC confers protection to HMLER cells againstanoikis, a form of apoptosis triggered upon anchorage-independent growth. Eventhough Notch-IC cooperates with oncogenic Ras HMLER cells to initiate tumors in vivo, they form well encapsulated, non-metastatictumors. Inhibition of Notch signaling, however, reverts the EMT phenotype of Sum1315 breast cancer cell line,as detected by increase in epithelial E-cadherin and loss of fibroblastic marker, vimentin. In order to assess whether the observed Notch-Ras cooperation in transformation of HMLE cells in vitro also holds true in vivo innaturally arising breast tumors, immunohistochemical analysis was undertaken. While in normal breast tissueactivated Notch, its downstream target Hes5, or phospho forms of Erk1/2 were not detected, abundant amounts of all these proteins were detected in the same areas within breast cancer tissue. This suggests that the Notch-Ras cooperation might indeed be involved in initiating breast carcinogenesis as it occurs in vivo.


Descriptors :   *BREAST CANCER , TISSUES(BIOLOGY) , HUMANS , PROTEINS , NEOPLASMS , IN VITRO ANALYSIS , SIGNALS , LIGANDS , LOW LEVEL , INHIBITION , ONCOGENESIS , IN VIVO ANALYSIS , CELLS(BIOLOGY) , PATHOGENESIS , MAMMARY GLANDS , IMMUNOCHEMISTRY , HISTOCHEMISTRY , EXPLOSIVES INITIATORS


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE