title: Expression of tripartite motif-containing protein 28 in primary breast carcinoma predicts metastasis and is involved in the stemness, chemoresistance, and tumor growth.
abstract: The prediction of who develops metastasis has been the most difficult aspect in the management of breast cancer patients. The lymph node metastasis has been the most useful predictor of prognosis and patient management. However, a good proportion of patients with lymph node positivity remain disease free for 5 years or more, while about a third of those who were lymph node negative develop distant metastasis within the same period. This warrants a robust biomarker(s), preferably gene expression based. In order to elucidate gene-based biomarkers for prognosis of breast cancers, gene expression profiling of primary tumors and follow-up for over 5 years has been performed. The analysis revealed a network of genes centered around the tripartite motif-containing protein 28 as an important indicator of disease progression. Short hairpin RNA-mediated knockdown of tripartite motif-containing protein 28 in breast cancer cells revealed a decreased expression of epithelial-to-mesenchymal transition markers and increased expression of epithelial markers, decreased migration and invasion, and increased chemosensitivity to doxorubicin, 5-fluorouracil, and methotrexate. Furthermore, knockdown of tripartite motif-containing protein 28 resulted in the decrease of stemness as revealed by sphere formation assay as well as decreased expression of CD44 and Bmi1. Moreover, tripartite motif-containing protein 28 knockdown significantly reduced the tumor size and lung metastasis in orthotopic tumor xenograft assay in immunocompromised mice. The tumor size was further reduced when these mice were treated with doxorubicin. These data provide evidence for tripartite motif-containing protein 28 as a biomarker and a potential therapeutic target for breast cancer.
authors.affiliation: 1 Indian Institute of Science, Bangalore, India.
authors.forename: Surekha
authors.initials: S
authors.lastname: Damineni
authors.affiliation: 2 Strand Life Sciences, Bangalore, India.
authors.forename: Sai A
authors.initials: SA
authors.lastname: Balaji
authors.affiliation: 1 Indian Institute of Science, Bangalore, India.
authors.forename: Abhijith
authors.initials: A
authors.lastname: Shettar
authors.affiliation: 2 Strand Life Sciences, Bangalore, India.
authors.forename: Swetha
authors.initials: S
authors.lastname: Nayanala
authors.affiliation: 1 Indian Institute of Science, Bangalore, India.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Kumar
authors.affiliation: 1 Indian Institute of Science, Bangalore, India.
authors.forename: Banavathy S
authors.initials: BS
authors.lastname: Kruthika
authors.affiliation: 2 Strand Life Sciences, Bangalore, India.
authors.forename: Kalyanasundaram
authors.initials: K
authors.lastname: Subramanian
authors.affiliation: 3 Kidwai Institute of Oncology, Bangalore, India.
authors.forename: M
authors.initials: M
authors.lastname: Vijayakumar
authors.affiliation: 3 Kidwai Institute of Oncology, Bangalore, India.
authors.forename: Geetashree
authors.initials: G
authors.lastname: Mukherjee
authors.affiliation: 2 Strand Life Sciences, Bangalore, India.
authors.forename: Vaijayanti
authors.initials: V
authors.lastname: Gupta
authors.affiliation: 1 Indian Institute of Science, Bangalore, India.
authors.forename: Paturu
authors.initials: P
authors.lastname: Kondaiah
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D051379:Mice; D009362:Neoplasm Metastasis; D012097:Repressor Proteins / Q000032:analysis / Q000502:physiology*; D000076183:Tripartite Motif-Containing Protein 28
chemical_list: C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D012097:Repressor Proteins; D004317:Doxorubicin; C101116:TRIM28 protein, human; D000076183:Tripartite Motif-Containing Protein 28
keywords: Tripartite motif-containing protein 28; chemoresistance; epithelial-to-mesenchymal transition; microarray; stemness