title: K-ras mutations and mucin profile in preneoplastic lesions and colon tumors induced in rats by 1,2-dimethylhydrazine.
abstract: K-ras and mucin profile variations, associated with intestinal carcinogenesis, were studied in the preneoplastic lesions, mucin-depleted foci (MDF) and aberrant crypt foci (ACF), and in colonic tumors induced in rats by 1,2-dimethylhydrazine (DMH). The frequency of lesions with K-ras mutations was 23% (3/13), 5.5% (1/18) and 100% (14/14) in MDF, tumors and ACF, respectively. Two of three MDF mutated in K-ras also carried a missense mutation in Apc. We also tested the expression of MUC2, a mucin abundantly expressed in normal colon and M1/MUCA5C, up-regulated in colon carcinogenesis, using immunohistochemistry. MDF and tumors showed a dramatic reduction in the expression of MUC2, whereas ACF showed only a slight reduction. The expression of M1/MUC5AC was almost absent in normal mucosa, but was increased in all the lesions (MDF, tumors and ACF). The expression of the intestinal trefoil factor (ITF), a marker of goblet cell lineage, was reduced in MDF and tumors compared to normal mucosa but not in ACF. In conclusion, although K-ras mutations are present in all ACF, they are less frequent in MDF and tumors; M1/MUC5AC is a marker associated with all preneoplastic events while the reduction of MUC2 and ITF expression is selectively associated with more advanced lesions such as MDF and tumors.
authors.affiliation: Department of Pharmacology, University of Florence, Florence, Italy.
authors.forename: Angelo Pietro
authors.initials: AP
authors.lastname: Femia
authors.forename: Elena
authors.initials: E
authors.lastname: Tarquini
authors.forename: Maddalena
authors.initials: M
authors.lastname: Salvadori
authors.forename: Stefania
authors.initials: S
authors.lastname: Ferri
authors.forename: Augusto
authors.initials: A
authors.lastname: Giannini
authors.forename: Piero
authors.initials: P
authors.lastname: Dolara
authors.forename: Giovanna
authors.initials: G
authors.lastname: Caderni
mesh_terms: D019813:1,2-Dimethylhydrazine / Q000633:toxicity*; D000818:Animals; D002471:Cell Transformation, Neoplastic; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D017491:Genes, APC / Q000502:physiology; D011905:Genes, ras / Q000235:genetics*; D007124:Immunoenzyme Techniques; D008297:Male; D009077:Mucins / Q000172:deficiency*; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation / Q000235:genetics*; D010455:Peptides / Q000378:metabolism; D011230:Precancerous Conditions / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D000071164:Trefoil Factor-2
chemical_list: D009077:Mucins; D009153:Mutagens; D010455:Peptides; D000071164:Trefoil Factor-2; D019813:1,2-Dimethylhydrazine