GT198 Mutation from common Progenitor Cells of different types of Stromal Cells in Breast Tissue function as Early Indicator of Breast Cancer

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GT198 Mutation from common Progenitor Cells of different types of Stromal Cells in Breast Tissue function as Early Indicator of Breast Cancer

March 21, 2016 by 2012pharmaceutical

GT198 Mutation from common Progenitor Cells of different types of Stromal Cells in Breast Tissue function as Early Indicator of Breast Cancer

Reporter: Aviva Lev-Ari, PhD, RN

Cause to breast cancer found by

Nahid Mivechi, PhD, cell biologist & radiobiologist, a group leader at the Cancer Center and a study co-author;
Nita Maihle, PhD, an MCG cancer biologist, associate center director for education at the university’s Cancer Center and a study co-author;
Dr. Lan Ko, cancer biologist in the Department of Pathology at the Medical College of Georgia at Augusta University and at the Georgia Cancer Center at AU

Image Credit: Phil Jones

About 4 percent of familial breast cancers would include inherited mutations of GT198, which is also considered a causative gene in sporadic cases, Ko said.
Ko first cloned the human GT198 gene while a postdoctoral fellow at Harvard Medical School, and subsequent studies by her and others have shown it has multiple roles that also include regulating stem cells, cell suicide and turning other genes off and on.

Their studies, published in the American Journal of Pathology, were done on an international sampling from 254 cases of breast cancer in pre- and postmenopausal women.

Story Source:

The above post is reprinted from materials provided by Medical College of Georgia at Augusta University. Note: Materials may be edited for content and length.

Journal Reference:

Zheqiong Yang, Min Peng, Liang Cheng, Kimya Jones, Nita J. Maihle, Nahid F. Mivechi, Lan Ko. GT198 Expression Defines Mutant Tumor Stroma in Human Breast Cancer. The American Journal of Pathology, 2016; DOI: 10.1016/j.ajpath.2016.01.006

Abstract

Human breast cancer precursor cells remain to be elucidated. Using breast cancer gene product GT198 (PSMC3IP; alias TBPIP or Hop2) as a unique marker, we revealed the cellular identities of GT198 mutant cells in human breast tumor stroma. GT198 is a steroid hormone receptor coactivator and a crucial factor in DNA repair. Germline mutations in GT198 are present in breast and ovarian cancer families. Somatic mutations inGT198 are present in ovarian tumor stromal cells. Herein, we show that human breast tumor stromal cells carry GT198 somatic mutations and express cytoplasmic GT198 protein. GT198⁺ stromal cells share vascular smooth muscle cell origin, including myoepithelial cells, adipocytes, capillary pericytes, and stromal fibroblasts. Frequent GT198 mutations are associated with GT198⁺ tumor stroma but not with GT198⁻ tumor cells. GT198⁺ progenitor cells are mostly capillary pericytes. When tested in cultured cells, mutant GT198 induces vascular endothelial growth factor promoter, and potentially promotes angiogenesis and adipogenesis. Our results suggest that multiple lineages of breast tumor stromal cells are mutated in GT198. These findings imply the presence of mutant progenitors, whereas their descendants, carrying the sameGT198 mutations, are collectively responsible for forming breast tumor microenvironment. GT198 expression is, therefore, a specific marker of mutant breast tumor stroma and has the potential to facilitate diagnosis and targeted treatment of human breast cancer.

SOURCE

http://ajp.amjpathol.org/article/S0002-9440(16)00087-0/abstract

Cite This Page:

http://www.sciencedaily.com/releases/2016/03/160318111445.htm

Medical College of Georgia at Augusta University. “New gene identified as cause, early indicator of breast cancer.” ScienceDaily. ScienceDaily, 18 March 2016. .

New Gene Found as Early Indicator of Breast Cancer?

Mon, 03/21/2016 – 10:13am

Medical College of Georgia at Augusta University

The gene GT198, whether mutated by genetics and/or environmental factors, has strong potential as both as a way to diagnose breast cancer early and as a new treatment target, said Dr. Lan Ko, cancer biologist in the Department of Pathology at the Medical College of Georgia at Augusta University and at the Georgia Cancer Center at Augusta University.

Mutations of the gene are known to be present in both early onset breast and ovarian cancer. Now scientists have shown that the stem, or progenitor cells, which should ultimately make healthy breast tissue, can also have GT198 mutations that prompt them to instead make a perfect bed for breast cancer.

Their studies, published in the American Journal of Pathology, were done on an international sampling from 254 cases of breast cancer in pre- and postmenopausal women.

“This gene mutation can be in both the blood and the tumor tissue of patients, and in the tissue, it’s in high percentages,” said Ko, the study’s corresponding author. “We believe that once this gene is mutated, it induces the tumor to grow.”

SOURCE

http://www.rdmag.com/news/2016/03/new-gene-found-early-indicator-breast-cancer?et_cid=5187994&et_rid=461755519&location=top&et_cid=5187994&et_rid=461755519&linkid=http%3a%2f%2fwww.rdmag.com%2fnews%2f2016%2f03%2fnew-gene-found-early-indicator-breast-cancer%3fet_cid%3d5187994%26et_rid%3d%%subscriberid%%%26location%3dtop