title: Evidence that RASSF1C stimulation of lung cancer cell proliferation depends on IGFBP-5 and PIWIL1 expression levels.
abstract: RASSF1C is a major isoform of the RASSF1 gene, and is emerging as an oncogene. This is in contradistinction to the RASSF1A isoform, which is an established tumor suppressor. We have previously shown that RASSF1C promotes lung cancer cell proliferation and have identified RASSF1C target genes with growth promoting functions. Here, we further report that RASSF1C promotes lung cancer cell migration and enhances lung cancer cell tumor sphere formation. We also show that RASSF1C over-expression reduces the inhibitory effects of the anti-cancer agent, betulinic acid (BA), on lung cancer cell proliferation. In previous work, we demonstrated that RASSF1C up-regulates piwil1 gene expression, which is a stem cell self-renewal gene that is over-expressed in several human cancers, including lung cancer. Here, we report on the effects of BA on piwil1 gene expression. Cells treated with BA show decreased piwil1 expression. Also, interaction of IGFBP-5 with RASSF1C appears to prevent RASSF1C from up-regulating PIWIL1 protein levels. These findings suggest that IGFBP-5 may be a negative modulator of RASSF1C/ PIWIL1 growth-promoting activities. In addition, we found that inhibition of the ATM-AMPK pathway up-regulates RASSF1C gene expression.
authors.affiliation: Surgical Oncology Laboratory, Loma Linda VA Medical Center, Loma Linda, California, United States of America; Department of Surgery, Loma Linda University School of Medicine, Loma Linda, California, United States of America.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Reeves
authors.affiliation: Surgical Oncology Laboratory, Loma Linda VA Medical Center, Loma Linda, California, United States of America.
authors.forename: Matthew
authors.initials: M
authors.lastname: Firek
authors.affiliation: Musculoskeletal Disease Center, Loma Linda VA Medical Center, Loma Linda, California, United States of America.
authors.forename: Shin-Tai
authors.initials: ST
authors.lastname: Chen
authors.affiliation: Surgical Oncology Laboratory, Loma Linda VA Medical Center, Loma Linda, California, United States of America; Department of Surgery, Loma Linda University School of Medicine, Loma Linda, California, United States of America.
authors.forename: Yousef G
authors.initials: YG
authors.lastname: Amaar
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms; D053978:Pentacyclic Triterpenes; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D015398:Signal Transduction; D018874:Spheroids, Cellular; D014315:Triterpenes / Q000494:pharmacology; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism; D000094062:Betulinic Acid
chemical_list: D000970:Antineoplastic Agents; D060565:Argonaute Proteins; C495270:CTNNB1 protein, human; D006877:Hydroxamic Acids; D018975:Insulin-Like Growth Factor Binding Protein 5; C421088:PIWIL1 protein, human; D053978:Pentacyclic Triterpenes; D011720:Pyrazoles; D011743:Pyrimidines; C411762:RASSF1 protein, human; D014315:Triterpenes; D025521:Tumor Suppressor Proteins; D051176:beta Catenin; C516138:dorsomorphin; C012589:trichostatin A; D000094062:Betulinic Acid