Up-regulated gene expression of angiogenesis factors in post-chemotherapeutic lung cancer tissues determined by cDNA macroarray.
The differential expressions of hundreds of tightly transcriptionally controlled genes in freshly isolated human lung cancers and respective normal lung tissues were analyzed by the cDNA macroarray technique. Three lung cancer patients received pre-operative chemotherapy with cisplatin containing regimens. After chemotherapy, these patients underwent surgery, and poly (A)-RNA expressions of 588 genes in the samples prepared from the lung cancer and normal lung tissues were compared. These expressions of the 588 genes were demonstrated by spotting onto a filter. Histogram analysis of gene expression revealed the tumors to show commonly up-regulated expression of angiogenesis and invasion related genes and adhesion molecules such as fibroblast growth factor 3 (FGFR3), matrix metalloproteinase (MMP)15, 16 and 10, integrin beta 4, integrin alpha 9, endonexin, and several types of collagens. Thus, post-chemotherapeutic tissues from lung cancer parents are characterized by remarkable up-regulation of molecules related to angiogenesis, invasion and adhesion. Tree view showed close clustering of angiogenesis related genes. Furthermore, when the angiogenesis related genes were selected and clustered, they were categorized into three groups depending upon gene expression profiles. These results suggest that angiogenesis related molecules are suitable candidates for target-based therapeutics and angiogenesis inhibitors are expected to be effective in lung cancer patients pretreated with chemotherapy.
Ohira
Tatsuo
T
First Department of Surgery, Tokyo Medical University, Tokyo 106-0023, Japan.
Akutagawa
Shigeru
S
Usuda
Jitsuo
J
Nakamura
Takashi
T
Hirano
Takashi
T
Tsuboi
Masahiro
M
Nishio
Kazuto
K
Taguchi
Fumiko
F
Ikeda
Norihido
N
Nakamura
Haruhiko
H
Konaka
Chimori
C
Saijo
Nagahiro
N
Kato
Harubumi
H
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D043925:Angiogenesis Inducing Agents / Q000096:biosynthesis / Q000235:genetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D004273:DNA, Neoplasm / Q000032:analysis; D051518:Fibroblast Growth Factor 3; D005346:Fibroblast Growth Factors / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011061:Poly A / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
D043925:Angiogenesis Inducing Agents; D004273:DNA, Neoplasm; C496444:FGF3 protein, human; D051518:Fibroblast Growth Factor 3; D016023:Integrins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011061:Poly A; D005346:Fibroblast Growth Factors; D003094:Collagen; D020782:Matrix Metalloproteinases