Altered Protein Expression Indicates Malignant Phenotype

Biological samples taken from patients' breast tumor tissue were analyzed for differential protein expression by two-dimensional gel electrophoresis followed by mass spectrometry and Western blot analysis.

Scientists at the Florida State University (Tallahassee, FL, USA; www.fsu.edu) microdissected samples from breast tissue to ascertain the protein expression of estrogen receptors (ER). Sections were immunohistochemically stained for ERα and different proliferation markers. Proteins were identified utilizing Matrix-Assisted Laser Desorption-Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF–MS).

Proteins extracted from 150,000 microdissected ERα positive and ERα negative breast cancer cells shows that ERα negative cells have reduced protein expression although there are three proteins exclusively expressed by the ERα negative cells. The significant findings are that the microdissected ER negative cells express 12.6 times less cellular retinoic acid-binding protein 1, a protein involved in cellular differentiation, and 4.1 times less nucleoside diphosphate kinase A or nm23-H1, a metastasis suppressor, and express fewer proteins than adjacent ER positive cells.

In a complementary study, the scientists accentuated their work on the stromal cells, which may play a larger role in the spread of cancer than was previously known. Measuring the number and amount of immunoreactive and metastasis-suppressing proteins that they produce could provide an early indication of how likely the cancer is to metastasize. Advanced analyses of normal stromal cells and reactive, or tumor-associated, stromal cells in prostate tissue showed key differences in the patterns of proteins that were expressed by each.

Qing-Xiang Sang, PhD the lead author of the study, said, "Biomarkers are indicators of certain biological and pathological processes that are occurring, such as cancer. If we can identify new and more accurate biomarkers that offer even earlier glimpses of these diseases, we stand a better chance of offering patients the most customized treatment possible, then, being able to monitor closely their progress, provide follow-up treatment as needed. With earlier diagnosis and treatment, the end result will hopefully be fewer people dying from these cancers.” The study was published online in July 2010, in the journal Clinical and Experimental Metastasis.

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