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Abstract

Grant Number: 5F32CA094788-02
Project Title: Identification of Receptor for Tumor Suppressor HIN-1
PI Information:NameEmailTitle
PORTER, DALE A. dale_porer@dfci.harvard.edu RESEARCH BIOLOGIST

Abstract: DESCRIPTION (provided by applicant): The overall objective of the proposed research is to isolate and characterize a receptor for HIN-1 (High In Normal-1). HIN-1 is a putative tumor suppressor gene recently identified using SAGE (Serial Analysis of Gene Expression) to compare gene expression profiles in normal and DCIS (ductal carcinoma in-situ, an early-stage breast tumor) mammary epithelial cells. HIN-1 appears to be a novel cytokine that is significantly down-regulated in 94 percent of human breast carcinomas. The first specific aim of the proposed research is to identify a receptor for HIN-1 using an expression cloning technique. An expression library generated from HIN-1 responsive mammary epithelial cells will be screened with alkaline phosphatase-tagged HIN-1. Specific aim 2 of the proposed research is to (A) confirm that HIN-1 binds directly to the isolated receptor by performing a co-precipitation assay, and (B) determine the affinity of HIN-1 for the isolated receptor by performing whole cell binding analysis. Specific aim 3 is to determine distribution of the HIN-1 receptor in breast cancer cell lines and in normal versus DCIS mammary epithelium using real-time quantitative PCR and in-situ hybridization. Identification and characterization of a HIN-1 receptor is the first step necessary to begin characterization of HIN-1 signal reception and transduction, and these studies may further suggest how loss of this signal may contribute to breast tumor progression.

Public Health Relevance:
This Public Health Relevance is not available.

Thesaurus Terms:
neoplasm /cancer genetics, receptor, tumor suppressor gene, tumor suppressor protein
breast neoplasm, gene expression, genetic library, mammary epithelium, protein structure function
clinical research, human tissue, immunoprecipitation, in situ hybridization, molecular cloning, northern blotting, polymerase chain reaction, postdoctoral investigator, serial analysis of gene expression, tissue /cell culture

Institution: DANA-FARBER CANCER INSTITUTE
44 BINNEY ST
BOSTON, MA 02115
Fiscal Year: 2003
Department:
Project Start: 01-SEP-2002
Project End: 09-JUL-2004
ICD: NATIONAL CANCER INSTITUTE
IRG: ZRG1


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