'Basal-like' breast cancer does not originate from basal stem cells

Sep 02, 2010

New research uncovers a case of mistaken identity that may have a significant impact on future breast cancer prevention and treatment strategies. The study, published by Cell Press in the September 3rd issue of the journal Cell Stem Cell, suggests that despite their "stem cell-like" characteristics, most aggressive breast tumors are not derived from normal mammary gland stem cells.

The glandular tissue of the breast contains two main cell types, outer "basal" cells and inner "luminal" cells. The basal layer consists mostly of differentiated cells with a small population of mammary . The luminal layer contains differentiated cells and several types of cells which are intermediates between the luminal cells and stem cells. The different cell types can be identified and separated on the basis of specific molecular markers.

"In , it has been proposed that different tumor subtypes may originate from different stem and intermediate cells, with more aggressive 'basal-like' breast cancers originating from basal stem cells and less aggressive breast cancers from the luminal intermediates," explains senior study author, Dr. Matthew J. Smalley from The Breakthrough Breast Cancer Research Centre at the Institute of Cancer Research in London. "Strikingly, the vast majority of with mutations in BRCA1, a breast cancer , have basal-like characteristics, suggesting a stem cell origin."

More recently, however, it was demonstrated that increases in abnormal luminal intermediate cells are associated with BRCA1 mutations and that there are similarities between the genes switched on in normal human luminal intermediate cells and basal-like breast cancer cells. "To resolve the true origin of BRCA1 breast cancer, we designed the first direct comparison of the effects of creating identical BRCA1-associated tumor predisposing events in basal stem versus luminal intermediate cells," says Dr. Smalley.

Specifically, the researchers deleted the BRCA1 gene in mouse basal stem cells or luminal intermediate cells. They discovered that although BRCA1 deletion caused tumors to form from both basal stem cells and luminal intermediate cells, only the latter had features that were identical to both human BRCA1 tumors and the majority of human basal-like breast cancers not associated with BRCA1 mutations.

Taken together, these findings suggest that the majority of so-called basal-like breast cancers are derived from luminal intermediate cells and not from basal stem cells as was originally expected. "Our results highlight luminal intermediate cells as a key to understanding the origins of basal-like breast cancer," concludes Dr. Smalley. "This has important implications for treatment and prevention strategies for this aggressive disease."

Explore further: Endogenous hormones improve breast cancer risk models

add to favorites email to friend print save as pdf

Related Stories

Stem cell 'daughters' lead to breast cancer

Aug 02, 2009

Walter and Eliza Hall Institute scientists have found that a population of breast cells called luminal progenitor cells are likely to be responsible for breast cancers that develop in women carrying mutations ...

Cell of origin identified for common type of breast cancer

Jan 19, 2010

A study by researchers at Tufts University School of Medicine, the Sackler School of Graduate Biomedical Sciences at Tufts, and Tufts Medical Center improves our current understanding of the origins of breast cancer. The ...

Herceptin targets breast cancer stem cells

Jul 09, 2008

A gene that is overexpressed in 20 percent of breast cancers increases the number of cancer stem cells, the cells that fuel a tumor's growth and spread, according to a new study from the University of Michigan Comprehensive ...

BRCA1 mutation linked to breast cancer stem cells

Jan 31, 2008

A new study may explain why women with a mutation in the BRCA1 gene face up to an 85 percent lifetime risk of breast cancer. Researchers from the University of Michigan Comprehensive Cancer Center found that BRCA1 plays a ...

Recommended for you

Endogenous hormones improve breast cancer risk models

16 hours ago

(HealthDay)—Inclusion of endogenous hormones in prediction models improves prediction of invasive breast cancer risk in postmenopausal women, according to a study published online Aug. 18 in the Journal of ...

Novel oncogenic RET mutation found in small cell lung cancer

17 hours ago

For the first time an oncogenic somatic mutation at amino acid 918 in the RET (rearranged during transfection) protein has been identified in small cell lung cancer (SCLC) tumors and enforced expression of this mutation within ...

User comments : 0