Accession Number:

ADA300951

Title:

In Vivo Transcriptional Regulation of the Human HMG-1/Y Gene as it Relates to the Progression of Breast Cancer.

Descriptive Note:

Final rept. 8 Sep 94-31 Jul 95,

Corporate Author:

WASHINGTON STATE UNIV PULLMAN DEPT OF GENETICS AND CELL BIOLOGY

Personal Author(s):

Report Date:

1995-08-23

Pagination or Media Count:

39.0

Abstract:

Increased HMG high mobility group-IY expression is correlated with more advanced cancers and with high metastatic potential. To determine what regulates the human HMG-IY gene in breast cancer, we studied the expression of the HMG-IY gene in two human breast cancer cell lines MCVI cells which are estrogen receptor positive and Hs578T cells which are estrogen receptor negative. HMG-IY expression was studied in the presence and absence of b-estradiol and epidermal growth factor EGF. No increase in HMG-IY messenger RNA was observed in b-estradiol or BGF treated MCF7 cells. In contrast, in the more metastatic Hs578T cell line there is a dramatic increase in HMG-bY mRNA expression, up to twenty-three fold, when treated with EGF. HMG-IY mRNA expression was further characterized in the EGF treated 11s578T cells using primer extensions, which showed that two of the multiple possible HMG-IY transcripts are induced. HMG-IY mRNA is very stable with a u2- 30 hours. Nuclear run- off transcription assays demonstrated an increase in the transcription rate of the HMG-IY gene in the presence of EGF. Western blots of protein extracted from Hs578T cells induced with EGF showed HMG-IY protein levels increased concurrently with the mRNA. The HMG-IY protein functions as an architectural transcription factor, thus the EGF induction of HMG-IY potentially provides a novel mechanism for a global alteration of gene expression in cancerous cells by a growth factorkinase signalling pathway.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE