Disease relevance of LSM1

• By using a Brome mosaic virus (BMV)-Saccharomyces cerevisiae system, we previously showed that the cellular Lsm1p-7p/Pat1p/Dhh1p decapping-activator complex functions in BMV RNA translation and replication [1].
• Thus, LSM1, BAG4, and C8orf4 are breast cancer oncogenes that can work in combination to influence the transformed phenotype in human mammary epithelial cells [2].
• We have searched for genes differentially expressed in advanced prostate cancers using cDNA-representational difference analysis, and thereby isolated the Lsm1 as one of down-regulated gene [3].
• CaSm (cancer-associated Sm-like) was originally identified based on elevated expression in pancreatic cancer and in several cancer-derived cell lines [4].
• We have recently shown that the cancer-associated Sm-like protein (CaSm) is overexpressed in human pancreatic adenocarcinoma (PC) [5].

High impact information on LSM1

• To examine the oncogenic role of LSM1, we overexpressed this gene in MCF10A mammary epithelial cells and inhibited its production in the SUM44 breast cancer cell line, which has a natural amplification and overexpression of LSM1 [6].
• Down-regulation of Lsm1 is involved in human prostate cancer progression [3].
• No critical gene mutations were found in open reading frame of Lsm1 in prostate cancers examined by PCR-SSCP analysis, including localised and refractory cancers [3].
• With human prostate cancers, almost all of informative prostatectomised cases without neoadjuvant therapy showed allelic retention in the Lsm1 region, whereas refractory cancers frequently showed allelic loss in this region [3].
• We have recently identified the cancer-associated Sm-like (CaSm) oncogene, shown that it is overexpressed in 87% of human pancreatic cancer samples, and clearly demonstrated that it functions as a classic oncogene [7].

Biological context of LSM1

• We further showed that three of these genes (LSM1, BAG4, and C8orf4) induce transformed phenotypes when overexpressed in MCF-10A cells, and overexpression of these genes in combination influences the growth factor independence phenotype and the ability of the cells to grow under anchorage-independent conditions [2].
• In untreated cells, alpha-chemokines, proinflammatory cytokines, and genes associated with apoptosis, inflammation, and lipid biosynthesis were higher in CASM, whereas some beta-chemokines, metalloproteinase inhibitors, and IGFBPs were higher in SVSM [8].
• CONTEXT: The cancer associated Sm-like proto-oncogene mRNA has been found to be overexpressed in the majority of pancreatic adenocarcinomas and is necessary for the transformed phenotype in pancreatic cancer cell lines [9].
• To better understand the molecular mechanisms underlying functional differences among distinct SMC subtypes, we compared gene expression profiles and functional responses to oxidized low-density lipoprotein (OxLDL) and platelet-derived growth factor (PDGF) between cultured SMCs from human coronary artery (CASM) and saphenous vein (SVSM) [8].

Anatomical context of LSM1

• Both CD34+/CD33- and CD34+/CD33+ hematopoietic progenitor cells weakly expressed LSM-1 [10].
• Megakaryocytes did not express LSM-1 [10].
• In the erythroid lineage, normal erythroblasts expressed very low levels of LSM-1, while erythroid cell lines (K562 and HEL) did not [10].
• It was found that in the lymphoid lineage, T and B lymphocytes as well as NK cells expressed LSM-1, whereas terminally differentiated plasma cells did not [10].
• As for the myeloid lineage, immature myeloid cells expressed LSM-1, whereas terminally differentiated granulocytes and monocytes did not [10].

Associations of LSM1 with chemical compounds

• The specific strategy described here of derivatizing tyrosine side chains with a charged caging moiety should be generally applicable in the preparation of caged peptides that have a critical tyrosine residue (e.g., LSM1) or that have critical hydrophobic patches (e.g., RS-20) [11].

Other interactions of LSM1

• PCR1 assay using LSM1 & LSM2 primers that amplified 496 bp of the ssurRNA gene was more sensitive than the PCR2 method using JNB25 and JD396 primers that amplified 334 bp of a RAPD-derived marker [12].
• Lineage- and differentiation stage-specific expression of LSM-1 (LPAP), a possible substrate for CD45, in human hematopoietic cells [10].

Analytical, diagnostic and therapeutic context of LSM1

• MAIN OUTCOME MEASURES: Quantitative expression levels of cancer associated Sm-like mRNA were measured by real-time PCR [9].

References