Expression of prohibitin 3' untranslated region suppressor RNA alters morphology and inhibits motility of breast cancer cells.
The prohibitin 3' untranslated region (3'UTR) belongs to a novel class of non-coding regulatory RNAs. It arrests cell cycle progression by blocking G1-S transition in breast and other cancers. Our previous studies comparing MCF7 derived clones constitutively expressing a common allelic form of prohibitin RNA (UTR/C) to various controls demonstrated that it functions as a tumor suppressor. Here, we further characterized the morphology and motility of these transgenic breast cancer cells when grown in cell culture and on nude mice. In contrast to empty vector (EV) cells, UTR/C cells were observed to grow in an organized manner with more cell-cell contact and differentiate into structures with a duct-like appearance. Computer assisted cytometry to evaluate differences in nuclear morphology was performed on UTR/C and EV tissues from nude mice. Receiver operator curve areas generated using a logistic regression model were 0.8, indicating the ability to quantitatively distinguish UTR/C from EV tissues. Keratinocyte growth factor-induced motility experiments showed that migration of UTR/C cells was significantly reduced (80-90%) compared to EV cells. Together, these data indicate that this novel 3'UTR influences not only the tumorigenic phenotype but also may play a role in differentiation and migration of breast cancer cells.
Manjeshwar
Sharmila
S
InterGenetics, Inc. and Program in Immunobiology and Cancer, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Lerner
Megan R
MR
Zang
Xiao-Ping
XP
Branam
Dannielle E
DE
Pento
J Thomas
JT
Lane
Mary M
MM
Lightfoot
Stan A
SA
Brackett
Daniel J
DJ
Jupe
Eldon R
ER
D020413:3' Untranslated Regions; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D048430:Cell Shape; D005260:Female; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D018715:Microscopy, Video; D000091402:Prohibitins; D012313:RNA / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D014183:Transplantation, Heterologous
D020413:3' Untranslated Regions; C496453:FGF7 protein, human; C496454:Fgf7 protein, mouse; D000091402:Prohibitins; D012097:Repressor Proteins; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D012313:RNA