US2010144830A1PendingUtilityA1
Cancer cell identification marker and cancer cell proliferation inhibitor
Est. expirySep 19, 2026(~0.2 yrs left)· nominal 20-yr term from priority
Inventors:Masahiko Kuroda
A61K 31/7088C12Q 1/6886C12N 2310/11C12N 2310/14C12Q 2600/136A61P 35/02C12Q 2600/158G01N 33/5011C12N 15/113A61P 35/00G01N 33/57595
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Claims
Abstract
Disclosed is an identification marker which can be utilized for detection of various human cancer cells and whose expression closely relates to malignant alteration of cells, and compositions for human cancer treatment which are based on suppression of cancer cell proliferation through inhibition of expression of the identification marker. The marker is human heterochromatin protein 1γ (HP1γ), and the compositions for cancer treatment comprises one or more agents which suppresses the expression of human HP1γ gene, such as siRNAs to human HP1γ.
Claims
exact text as granted — not AI-modified1 . A method for identifying a cell presented for examination as either being a cancer cell or a non-cancer cell, comprising the steps of
detecting of expression of HP1γ in the cell presented for examination, and identifying the cell as being a cancer cell if expression of HP1γ is detected in the cell, and as being a non-cancer cell if no expression of HP1γ is detected in the cell.
2 . The method according to claim 1 , wherein the cancer cell is an epithelial cancer cell and/or a non-epithelial cancer cell of a mammalian animal including a human, and wherein the HP1γ is HP1γ of the mammalian animal.
3 . The method according to claim 1 , wherein the cell presented for examination is a human cell and the HP1γ is human HP1γ.
4 . A cancer cell proliferation inhibitor agent consisting of an inhibitor compound of HP1γ gene expression.
5 . The cancer cell proliferation inhibitor agent according to claim 4 , wherein the cancer cell is an epithelial cancer cell and/or a non-epithelial cancer cell of a mammalian animal including a human, and wherein the HP1γ is HP1γ of the mammalian animal.
6 . The cancer cell proliferation inhibitor agent according to claim 4 , wherein the inhibitor compound of HP1γ gene expression is an siRNA specific to HP1γ gene or an antisense DNA specific to HP1γ gene.
7 . The cancer cell proliferation inhibitor agent according to claim 4 , wherein the cancer cell is a human cancer cell, and wherein the HP1γ gene is human HP1γ gene.
8 . The cancer cell proliferation inhibitor agent according to claim 7 , wherein the inhibitor compound of HP1γ gene expression is an siRNA comprising at least one of the double-stranded RNAs #1 to #106 each of which comprises a corresponding RNA strand set forth in the 5′ to 3′ direction in the following Tables 1A to 1F:
TABLE 1A
SEQ ID
NO:
Sequence
#1
39
CAACAAAACUACAUUGCAA
192
UUGCAAUGUAGUUUUGUUG
#2
127
AAAACAGAAUGGAAAGAGU
193
ACUCUUUCCAUUCUGUUUU
#3
40
AAACAGAAUGGAAAGAGUA
194
UACUCUUUCCAUUCUGUUU
#4
128
AACAGAAUGGAAAGAGUAA
195
UUACUCUUUCCAUUCUGUU
#5
41
CAGAAUGGAAAGAGUAAAA
196
UUUUACUCUUUCCAUUCUG
#6
129
AAAAAGUUGAAGAGGCAGA
197
UCUGCCUCUUCAACUUUUU
#7
130
AGUUGAAGAGGCAGAGCCU
198
AGGCUCUGCCUCUUCAACU
#8
43
UUGAAGAGGCAGAGCCUGA
199
UCAGGCUCUGCCUCUUCAA
#9
44
AGGCAGAGCCUGAAGAAUU
200
AAUUCUUCAGGCUCUGCCU
#10
45
GGCAGAGCCUGAAGAAUUU
201
AAAUUCUUCAGGCUCUGCC
#11
46
CUGAAGAAUUUGUCGUGGA
202
UCCACGACAAAUUCUUCAG
#12
47
UGAAGAAUUUGUCGUGGAA
203
UUCCACGACAAAUUCUUCA
#13
48
AAGAAUUUGUCGUGGAAAA
204
UUUUCCACGACAAAUUCUU
#14
131
AGAAUUUGUCGUGGAAAAA
205
UUUUUCCACGACAAAUUCU
#15
132
UGUCGUGGAAAAAGUACUA
206
UAGUACUUUUUCCACGACA
#16
133
UGGAAAAAGUACUAGAUCG
207
CGAUCUAGUACUUUUUCCA
#17
49
GGAAAAAGUACUAGAUCGA
208
UCGAUCUAGUACUUUUUCC
#18
50
AGUACUAGAUCGACGUGUA
209
UACACGUCGAUCUAGUACU
TABLE 1B
SEQ ID
NO:
Sequence
#19
51
AGAUCGACGUGUAGUGAAU
210
AUUCACUACACGUCGAUCU
#20
134
GACGUGUAGUGAAUGGGAA
211
UUCCCAUUCACUACACGUC
#21
52
ACGUGUAGUGAAUGGGAAA
212
UUUCCCAUUCACUACACGU
#22
53
AGUGAAUGGGAAAGUGGAA
213
UUCCACUUUCCCAUUCACU
#23
135
GUGAAUGGGAAAGUGGAAU
214
AUUCCACUUUCCCAUUCAC
#24
54
UGAAUGGGAAAGUGGAAUA
215
UAUUCCACUUUCCCAUUCA
#25
136
UUCCUGAAGUGGAAGGGAU
216
AUCCCUUCCACUUCAGGAA
#26
137
UCCUGAAGUGGAAGGGAUU
217
AAUCCCUUCCACUUCAGGA
#27
138
CUGAAGUGGAAGGGAUUUA
218
UAAAUCCCUUCCACUUCAG
#28
139
GUGGAAGGGAUUUACAGAU
219
AUCUGUAAAUCCCUUCCAC
#29
140
UGGAAGGGAUUUACAGAUG
220
CAUCUGUAAAUCCCUUCCA
#30
141
AUUUACAGAUGCUGACAAU
221
AUUGUCAGCAUCUGUAAAU
#31
142
GCUGACAAUACUUGGGAAC
222
GUUCCCAAGUAUUGUCAGC
#32
143
UGACAAUACUUGGGAACCU
223
AGGUUCCCAAGUAUUGUCA
#33
55
CUUGGGAACCUGAAGAAAA
224
UUUUCUUCAGGUUCCCAAG
#34
144
UUGGGAACCUGAAGAAAAU
225
AUUUUCUUCAGGUUCCCAA
#35
56
CAGAAUUGAUUGAAGCGUU
226
AACGCUUCAAUCAAUUCUG
#36
57
AGAAUUGAUUGAAGCGUUU
227
AAACGCUUCAAUCAAUUCU
#37
145
UGAUUGAAGCGUUUCUUAA
228
UUAAGAAACGCUUCAAUCA
TABLE 1C
SEQ ID
NO:
Sequence
#38
146
GUUUCUUAACUCUCAGAAA
229
UUUCUGAGAGUUAAGAAAC
#39
58
UCAGAAAGCUGGCAAAGAA
230
UUCUUUGCCAGCUUUCUGA
#40
59
CAGAAAGCUGGCAAAGAAA
231
UUUCUUUGCCAGCUUUCUG
#41
147
AGAAAGCUGGCAAAGAAAA
232
UUUUCUUUGCCAGCUUUCU
#42
60
GAAAGCUGGCAAAGAAAAA
233
UUUUUCUUUGCCAGCUUUC
#43
148
UGGCAAAGAAAAAGAUGGU
234
ACCAUCUUUUUCUUUGCCA
#44
61
GCAAAGAAAAAGAUGGUAC
235
GUACCAUCUUUUUCUUUGC
#45
62
CAAAGAAAAAGAUGGUACA
236
UGUACCAUCUUUUUCUUUG
#46
149
AAUCUUUAUCUGACAGUGA
237
UCACUGUCAGAUAAAGAUU
#47
63
GUGAAUCUGAUGACAGCAA
238
UUGCUGUCAUCAGAUUCAC
#48
150
GAAUCUGAUGACAGCAAAU
239
AUUUGCUGUCAUCAGAUUC
#49
151
GAUGACAGCAAAUCAAAGA
240
UCUUUGAUUUGCUGUCAUC
#50
152
GACAGCAAAUCAAAGAAGA
241
UCUUCUUUGAUUUGCUGUC
#51
64
ACAGCAAAUCAAAGAAGAA
242
UUCUUCUUUGAUUUGCUGU
#52
153
CAGCAAAUCAAAGAAGAAA
243
UUUCUUCUUUGAUUUGCUG
#53
154
GCAAAUCAAAGAAGAAAAG
244
CUUUUCUUCUUUGAUUUGC
#54
66
UCAAAGAAGAAAAGAGAUG
245
CAUCUCUUUUCUUCUUUGA
#55
155
GAAGAAAAGAGAUGCUGCU
246
AGCAGCAUCUCUUUUCUUC
#56
156
AGAAAAGAGAUGCUGCUGA
247
UCAGCAGCAUCUCUUUUCU
TABLE 1D
SEQ ID
NO:
Sequence
#57
67
GAAAAGAGAUGCUGCUGAC
248
GUCAGCAGCAUCUCUUUUC
#58
157
AAAGAGAUGCUGCUGACAA
249
UUGUCAGCAGCAUCUCUUU
#59
68
AAGAGAUGCUGCUGACAAA
250
UUUGUCAGCAGCAUCUCUU
#60
69
GCUGACAAACCAAGAGGAU
251
AUCCUCUUGGUUUGUCAGC
#61
158
CUGACAAACCAAGAGGAUU
252
AAUCCUCUUGGUUUGUCAG
#62
1
UGACAAACCAAGAGGAUUU
253
AAAUCCUCUUGGUUUGUCA
#63
159
ACCAAGAGGAUUUGCCAGA
254
UCUGGCAAAUCCUCUUGGU
#64
160
AGGAUUUGCCAGAGGUCUU
255
AAGACCUCUGGCAAAUCCU
#65
161
UGCCAGAGGUCUUGAUCCU
256
AGGAUCAAGACCUCUGGCA
#66
162
CCAGAGGUCUUGAUCCUGA
257
UCAGGAUCAAGACCUCUGG
#67
163
AGGUCUUGAUCCUGAAAGA
258
UCUUUCAGGAUCAAGACCU
#68
164
GUCUUGAUCCUGAAAGAAU
259
AUUCUUUCAGGAUCAAGAC
#69
165
UCUUGAUCCUGAAAGAAUA
260
UAUUCUUUCAGGAUCAAGA
#70
166
CCACAGACAGCAGUGGAGA
261
UCUCCACUGCUGUCUGUGG
#71
167
CACAGACAGCAGUGGAGAA
262
UUCUCCACUGCUGUCUGUG
#72
168
ACAGACAGCAGUGGAGAAU
263
AUUCUCCACUGCUGUCUGU
#73
70
AGACAGCAGUGGAGAAUUG
264
CAAUUCUCCACUGCUGUCU
#74
169
GUGGAGAAUUGAUGUUUCU
265
AGAAACAUCAAUUCUCCAC
#75
170
GAGAAUUGAUGUUUCUCAU
266
AUGAGAAACAUCAAUUCUC
TABLE 1E
SEQ ID
NO:
Sequence
#76
171
GAAUUGAUGUUUCUCAUGA
267
UCAUGAGAAACAUCAAUUC
#77
71
CUCAUGAAAUGGAAAGAUU
268
AAUCUUUCCAUUUCAUGAG
#78
172
CAUGAAAUGGAAAGAUUCA
269
UGAAUCUUUCCAUUUCAUG
#79
173
UGAAAUGGAAAGAUUCAGA
270
UCUGAAUCUUUCCAUUUCA
#80
174
GGAAAGAUUCAGAUGAGGC
271
GCCUCAUCUGAAUCUUUCC
#81
175
GAAAGAUUCAGAUGAGGCA
272
UGCCUCAUCUGAAUCUUUC
#82
176
AAGAUUCAGAUGAGGCAGA
273
UCUGCCUCAUCUGAAUCUU
#83
72
CAGACUUGGUGCUGGCGAA
274
UUCGCCAGCACCAAGUCUG
#84
177
AGACUUGGUGCUGGCGAAA
275
UUUCGCCAGCACCAAGUCU
#85
178
ACUUGGUGCUGGCGAAAGA
276
UCUUUCGCCAGCACCAAGU
#86
179
GGUGCUGGCGAAAGAGGCA
277
UGCCUCUUUCGCCAGCACC
#87
180
UGGCGAAAGAGGCAAAUAU
278
AUAUUUGCCUCUUUCGCCA
#88
73
GCGAAAGAGGCAAAUAUGA
279
UCAUAUUUGCCUCUUUCGC
#89
74
CGAAAGAGGCAAAUAUGAA
280
UUCAUAUUUGCCUCUUUCG
#90
181
AGGCAAAUAUGAAGUGUCC
281
GGACACUUCAUAUUUGCCU
#91
182
GCAAAUAUGAAGUGUCCUC
282
GAGGACACUUCAUAUUUGC
#92
183
AAUAUGAAGUGUCCUCAAA
283
UUUGAGGACACUUCAUAUU
#93
184
CCUCAAAUUGUAAUUGCUU
284
AAGCAAUUACAAUUUGAGG
#94
185
AGAGAGACUAACUUGGCAU
285
AUGCCAAGUUAGUCUCUCU
and
TABLE 1F
SEQ ID
NO:
Sequence
#95
186
GAGAGACUAACUUGGCAUU
286
AAUGCCAAGUUAGUCUCUC
#96
187
GCAUUCUUGUCCAGAAGAU
287
AUCUUCUGGACAAGAAUGC
#97
188
GUCCAGAAGAUGAAGCUCA
288
UGAGCUUCAUCUUCUGGAC
#98
189
UCCAGAAGAUGAAGCUCAA
289
UUGAGCUUCAUCUUCUGGA
#99
75
CAGAAGAUGAAGCUCAAUA
290
UAUUGAGCUUCAUCUUCUG
#100
190
AGAAGAUGAAGCUCAAUAA
291
UUAUUGAGCUUCAUCUUCU
#101
83
GAUAAUCCCUUCAAGUUAA
292
UUAACUUGAAGGGAUUAUC
#102
84
CCAUACAUUUCAAGUGAAA
293
UUUCACUUGAAAUGUAUGG
#103
88
GACAAAUGCUAGUGUGUUU
294
AAACACACUAGCAUUUGUC
#104
89
GGGCCAUUCCUUAGCAAAA
295
UUUUGCUAAGGAAUGGCCC
#105
191
GGUCAUGAUGAAUGGAAUA
296
UAUUCCAUUCAUCAUGACC
#106
95
CAGCAAAAGCCAGGAAGAA
297
UUCUUCCUGGCUUUUGCUG
9 . The cancer cell proliferation inhibitor agent according to claim 8 , wherein the double-stranded RNAs are selected from the group consisting of the double-stranded RNAs set forth as #5, #17, #35, #62, #89, #101, #102, #103, #104, #105 and #106 in Tables 1A to 1F.
10 . The cancer cell proliferation inhibitor agent according to claim 8 , wherein the double-stranded RNAs are selected from the group consisting of the double-stranded RNAs set forth as #17, #62 and #89 in Tables 1A to 1F.
11 . The cancer cell proliferation inhibitor agent according to claim 8 , wherein the siRNA has two-base overhangs on its both ends.
12 . The cancer cell proliferation inhibitor agent according to claim 8 , wherein each of the overhangs is on the 3′ end of each of the strands forming the double-stranded RNA.
13 . A composition for the treatment of cancer in a mammal including a human comprising, in a pharmaceutically acceptable carrier, one or more of the cancer cell proliferation inhibitor agents according to claim 6 .
14 . The composition for the treatment of cancer according to claim 13 , wherein the cancer is cancer in a human, the HP1γ gene is human HP1γ gene, and the inhibitor compound of HP1γ gene expression is an siRNA specific to human HP1γ gene.
15 . The composition for the treatment of cancer in a human comprising, in a pharmaceutically acceptable carrier, one or more of the cancer cell proliferation inhibitor agents according to claim 8 .
16 . A method for the treatment of cancer in a mammal including a human comprising administering an effective amount of one or more of the cancer cell proliferation inhibitor agents according to claim 6 , in a pharmaceutically acceptable carrier, to the mammal including a human in need thereof.
17 . A method for the treatment of cancer in a human comprising administering an effective amount of one or more of the cancer cell proliferation inhibitor agents according to claim 8 , in a pharmaceutically acceptable carrier, to the human in need thereof.
18 . Use of one of the cancer cell proliferation inhibitor agents according to claim 8 , for the production of a composition for the treatment of human cancer.
19 . A method of screening for cancer cell proliferation inhibitor agents comprising the steps of;
bringing part of cancer cells into contact with candidate compounds, separately detecting expression of HP1γ gene in those cancer cells which were brought into contact with the candidate compounds and in those cancer cells which were not brought into contact with a candidate compound, determining whether or not HP1γ gene expression was inhibited in the cancer cells which were brought into contact with the candidate compounds by comparing the amount of expression of HP1γ gene in the cancer cells which were brought into contact with the candidate compounds with that in the cancer cells which were not brought into contact a candidate compound, selecting, as cancer cell proliferation inhibitor agents, those candidate compounds which were brought into contact with those cancer cells in which inhibition of the expression was found.Cited by (0)
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