Melphalan modulates the expression of E7-specific biomarkers in E7-Tg mice.
HPV oncoproteins are selectively retained and expressed in HPV infected carcinoma cells. The E7 oncoprotein interacts with the tumour suppressor Rb, and leads to the progression of oncogenesis. In a previous study, E7 biomarkers were identified in E7 Tg mice. In this study, in order to investigate whether a genotoxic carcinogen would modulate carcinogenesis in the E7-Tg mice, an anticancer drug, melphalan, was intraperitoneally injected into E7-Tg mice for eight weeks at two-day intervals and then genes and proteins were analysed using Omics approaches and RT-qPCR. RT-qPCR was performed to confirm whether E7 biomarkers would be modulated by melphalan treatment in E7-Tg mice, revealing that up-regulated E7 markers such as cyclin B1, CD166, and actin alpha1 were down-regulated, whereas expression of down-regulated E7 markers such as vimentin was restored by melphalan treatment. These results suggest that melphalan inhibits carcinogenesis via modulating E7-specific genes and proteins expressed in the lung tissues of E7 Tg mice.
Kim
Eun Jin
EJ
Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Hwayang-dong 1, Gwangjin-gu, Seoul 143-701, Korea.
Kim
Heejong
H
Lee
Sojung
S
Kang
Jeong Woo
JW
Lee
Dong Hun
DH
Choi
Hee Sook
HS
Kim
Jin Man
JM
Yang
Young
Y
Sheen
Yhun Yhong
YY
Park
Sue Nie
SN
Yoon
Do Young
DY
D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D020410:Activated-Leukocyte Cell Adhesion Molecule / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D056744:Cyclin B1 / Q000096:biosynthesis / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D007274:Injections, Intraperitoneal; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology*; D008297:Male; D008558:Melphalan / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D050725:Papillomavirus E7 Proteins / Q000096:biosynthesis* / Q000235:genetics; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000199:Actins; D020410:Activated-Leukocyte Cell Adhesion Molecule; D018906:Antineoplastic Agents, Alkylating; D014408:Biomarkers, Tumor; D056744:Cyclin B1; D050725:Papillomavirus E7 Proteins; D008558:Melphalan