The gene SIATL-1 encoding a new sialyltransferase (STM) is down regulated or absent in breast cancer tumor cells
Contributed by: Ecaterina Facina & Alexander Vena
Animals, Asia, Cancer, Europe, Fundamental research, Gene expression, Historical figure, Lab, Medicine, Meiosis, Molecular biology, North America, Woman
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Sotiropoulou, Georgia, et al. “Identification and Functional Characterization of a Human GalNAc α2,6-Sialyltransferase with Altered Expression in Breast Cancer.” Molecular Medicine, vol. 8, no. 1, 2002, pp. 42–55., doi:10.1007/bf03402002.
Slide 1: Researcher’s Background
Ruth Sager was a research scientist and she had 2 different careers in non-nuclear or cytoplasmic genetics as well as the genetics of cancer. She almost developed the subject of non-Mendelian genetics and identified genes that have altered expression in breast cancers such as mammary serpin and maspin.
Biography in brief
Ruth Sager (1918-1997) is a American geneticist best known for her two different research careers in non nuclear or cytoplasmic genetics as well as cancer genetics. She received her Ph.D at Columbia University and continued her research there. Alongside her research, she also became a biology professor at Hunter College, worked at the Dana-Farber Cancer Institute, becoming the chief of cancer genetics, and she was also a genetics professor at Harvard Medical School. She had an extensive and impressive career. During her research she had a few findings:
- She showed that chloroplasts and mitochondria in cells of organisms contain genetic materials that synthesize proteins and other substances to regulate their own development.
- She identified genes that have altered expression in breast cancers such as mammary serpin and maspin.
- She almost developed the subject of non-Mendelian genetics.
Is (or was) their research under-valued because of their identity?
Slide 2: Research Overview
Take home message of study
Human gene SIATL-1 was found to repressed or even absent in breast cancer tissues in comparison with normal tissues. The SIATL-1 gene location was mapped along the long arm of chromosome 17 and its expression was compared between normal expression in healthy tissues and altered expression in monkey kidney COS-7 cells.
The ideogram shows the contents of chromosome 17, the chromosome which is used for chromosomal localization of the SIATL-1 gene. Six different intervals from this panel will allow genes to be assigned to a panel on this chromosome. Southern blot analysis of the gene encoding STM sialyltransferase revealed the existence of specific sequences of the SIATL-1 gene correlated with the presence of the region 17q23-qter. The bottom of the panel shows the presence (+) or the absence (-) of the specific sequences of the SIATL-1 gene in hybrid zones.
Slide 3: Key Research Points
The figure shows how the STM gene was discovered by using a technique called multiway differential display. Differential display allows a researcher to compare gene expression in many cell populations, all simultaneously. In this figure, lanes 76N and 70N represent total RNA from normal mammary epithelial strains, lanes 21PT and 21NT represent primary malignant tumor lines, lane MCF-7 represents metastatic ER+ malignant tumor lines and lanes 21MT-1, 21MT-2, MDA-MB-435 represent metastatic ER- malignant tumor lines. Each one of these lanes all replicate indefinitely in the culture used in this technique. Figure 1A shows the progression of tumor formation as a series of cell lines (21NT to 21MT-1), which was from a patient with breast cancer, which led to the discovery of the partial stm cDNA (125bp) is indicated by the arrow labelled ‘stm’, while the other arrow indicates another differentially expressed cDNA. Figure 1B (upper) shows Northern hybridizations to conform that each of the two expressions are the partial stm cDNA. This technique used the cloned and P-labeled partial STM as a probe which were then both cloned and sequenced independently. Figure 1B (lower) shows the two subunits (18S and 28S) of ribosomal RNA, with each lane containing 20 µg total RNA and then stained with ethidium bromide.
Breast cancer research is extremely relevant to this day. There is no definite cure or even a known cause as to what causes it. According to the government of Canada website, approximately 1 in 8 women are expected to develop breast cancer in her lifetime and 1 of 33 women with breast cancer is expected to die. The statistics don’t look too good as that means around 27 900 Canadian women will be diagnosed in a year. Therefore, research is important to help those women. Moreover, it seems as through this research can be applied to other tumors as well. For example, down regulation of STM was also found in prostate malignant tumor cells. The Canadian cancer society estimates that 1 in 9 Canadian men will develop prostate cancer in their lifetime and 1 in 29 will die from it. So again, this research can help so many people if it is furthered. The researches of the article state that this protein can be down regulated in multiple tumor cells, there just needs to be more research in comparing tumor vs normal cells.