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) : Holth, Laurel S.

PDF Url : ADA300951

Report Date : 23 AUG 1995

Pagination or Media Count : 39

Abstract : Increased HMG (high mobility group)-I;/Y expression is correlated with more advanced cancers and with high metastatic potential. To determine what regulates the human HMG-I/Y gene in breast cancer, we studied the expression of the HMG-I/Y gene in two human breast cancer cell lines: MCVI cells which are estrogen receptor positive and Hs578T cells which are estrogen receptor negative. HMG-I/Y expression was studied in the presence and absence of b-estradiol and epidermal growth factor (EGF). No increase in HMG-I/Y 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-I/Y mRNA expression was further characterized in the EGF treated 11s578T cells using primer extensions, which showed that two of the multiple possible HMG-I/Y transcripts are induced. HMG-I/Y mRNA is very stable with a u/2- 30 hours. Nuclear run- off transcription assays demonstrated an increase in the transcription rate of the HMG-I/Y gene in the presence of EGF. Western blots of protein extracted from Hs578T cells induced with EGF showed HMG-I/Y protein levels increased concurrently with the mRNA. The HMG-I/Y protein functions as an "architectural transcription factor", thus the EGF induction of HMG-I/Y potentially provides a novel mechanism for a global alteration of gene expression in cancerous cells by a growth factor/kinase signalling pathway.

Descriptors :   *GENES, *IN VIVO ANALYSIS, *MAMMARY GLANDS, *BREAST CANCER, MOBILITY, HIGH RATE, CELLS, PROTEINS, PRIMERS, ADAPTERS, SENSE ORGANS, EPIDERMIS, GROWTH(PHYSIOLOGY), ESTROGENS, METASTASIS.

Subject Categories : Anatomy and Physiology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE