Transduction of the SkBr3 breast carcinoma cell line with the HOXB7 gene induces bFGF expression, increases cell proliferation and reduces growth factor dependence.
Several melanomas, carcinomas, glioblastomas and leukemias showed coordinated expression of HOXB7 and bFGF with exception of the SkBr3 mammary carcinoma that was negative for both. Transduction of HOXB7 gene into SkBr3 cells, induced bFGF expression, increased growth rate, independence from serum withdrawal and ability to form colonies in semisolid medium. ELISA assay showed that most of bFGF was associated to cell lysate when cells were cultured at 1% serum whereas in cells kept to 10% serum bFGF was detected both within cell lysate or secreted into cell supernatants. Antisense oligos to bFGF inhibited the growth of cells cultured in 1%, indicating that beside the possible activation of additional genes other than bFGF by HOXB7 transduction, only bFGF induction accounts for the observed results. Moreover, since inhibition of cell proliferation occurred in cells kept in 1% but not 10% serum, a bFGF intracrine loop appears operative in serum starved SkBr3/HOXB7 cells. Also, these results further indicate bFGF as target of HOXB7.
Department of Hematology and Oncology, Istituto Superiore di Sanità, Rome, Italy.
A
A
Caré
A
A
Silvani
E
E
Meccia
G
G
Mattia
C
C
Peschle
M P
MP
Colombo
D000362:Agar / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D003470:Culture Media / Q000494:pharmacology; D017077:Culture Media, Conditioned / Q000737:chemistry; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D005801:Genes, Homeobox / Q000235:genetics*; D006133:Growth Substances / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000166:cytology / Q000378:metabolism
D003470:Culture Media; D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D006133:Growth Substances; C490538:HOXB7 protein, human; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D000362:Agar