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Human thyroid tumours, the puzzling lessons from E7 and RET/PTC3 transgenic mice.

Jin L, Burniat A, Dumont JE, Miot F, Corvilain B, Franc B - Br. J. Cancer (2008)

Bottom Line: There is an 'oncogene dependent' cellular signature, maintained at all studied ages in the E7 model, less in the RET/PTC3 model.The Tg-E7 model was less heterogeneous, with a dominant goitrous pattern.The solid tumour already described in the RET/PTC3 models associated with cribriform patterns, suggested 'PTC spindle cell changes' as in humans PTC rather than the equivalent of the solid human PTC.

View Article: PubMed Central - PubMed

Affiliation: Institut de Recherche Interdisciplinaire (IRIBHM), Faculté de Médecine, Université Libre de Bruxelles (ULB), Campus Erasme, Route de Lennik 808, B 1070 Bruxelles, Belgique. lingjin@ulb.ac.be

ABSTRACT
Human rearranged RET/PTC3 (papillary thyroid carcinoma) proto-oncogene and high-risk human papillomavirus (HPV) type 16 E7 oncogene induces in the mouse a neoplastic transformation of thyroid follicular cells. We present a detailed immuno-histological study (170 mouse thyroids: RET/PTC3, E7, wild type, 2- to 10-month-old) with cell cycle proliferation and signalling pathway indicators. The characteristics of both models are different. There is an 'oncogene dependent' cellular signature, maintained at all studied ages in the E7 model, less in the RET/PTC3 model. During tumour development a large heterogeneity occurred in the Tg-RET/PTC3 model within a same tumour or within a same thyroid lobe. The Tg-E7 model was less heterogeneous, with a dominant goitrous pattern. The solid tumour already described in the RET/PTC3 models associated with cribriform patterns, suggested 'PTC spindle cell changes' as in humans PTC rather than the equivalent of the solid human PTC. Proliferation and apoptosis in the two thyroid models are related to the causal oncogene rather than reflect a general tumorigenic process. The thyroids of RET/PTC3 mice appeared as a partial and transient model of human PTCs, whereas the Tg-E7 mice do not belong to the usual PTC type.

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Related in: MedlinePlus

Paraformaldehyde-fixed, paraffin-embedded and haematoxylin–eosin stained thyroid tissues from C57Bl/6, E7 and RET/PTC3. (A–C) 2, 6, and 10-month C57Bl/6 thyroids respectively; (D–F) 2-, 6-, 10-month E7 thyroids respectively; (G–I) 2-, 6-, 10-month RET/PTC3 respectively, (I) two lobes from the same mouse; (J and K) 2-, and 6-month RET/PTC3 with remodeling and cyst (diffuse sclerosing); upper right insert of J: macrophages infiltration, middle right insert of J: nuclear inclusion; low right insert of J: thick spindle-like cells in between follicles. Original magnification 2.5 × . Scale bar: 1 mm.
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fig1: Paraformaldehyde-fixed, paraffin-embedded and haematoxylin–eosin stained thyroid tissues from C57Bl/6, E7 and RET/PTC3. (A–C) 2, 6, and 10-month C57Bl/6 thyroids respectively; (D–F) 2-, 6-, 10-month E7 thyroids respectively; (G–I) 2-, 6-, 10-month RET/PTC3 respectively, (I) two lobes from the same mouse; (J and K) 2-, and 6-month RET/PTC3 with remodeling and cyst (diffuse sclerosing); upper right insert of J: macrophages infiltration, middle right insert of J: nuclear inclusion; low right insert of J: thick spindle-like cells in between follicles. Original magnification 2.5 × . Scale bar: 1 mm.

Mentions: At 2 months, WT mouse thyroids harboured cuboidal follicular cells lining small follicles (Figures 1A–C and 2A). The size of the follicles became heterogeneous at 6 months, with dominant large follicles lined by flat cells at 10 months (Figure 2B and C).


Human thyroid tumours, the puzzling lessons from E7 and RET/PTC3 transgenic mice.

Jin L, Burniat A, Dumont JE, Miot F, Corvilain B, Franc B - Br. J. Cancer (2008)

Paraformaldehyde-fixed, paraffin-embedded and haematoxylin–eosin stained thyroid tissues from C57Bl/6, E7 and RET/PTC3. (A–C) 2, 6, and 10-month C57Bl/6 thyroids respectively; (D–F) 2-, 6-, 10-month E7 thyroids respectively; (G–I) 2-, 6-, 10-month RET/PTC3 respectively, (I) two lobes from the same mouse; (J and K) 2-, and 6-month RET/PTC3 with remodeling and cyst (diffuse sclerosing); upper right insert of J: macrophages infiltration, middle right insert of J: nuclear inclusion; low right insert of J: thick spindle-like cells in between follicles. Original magnification 2.5 × . Scale bar: 1 mm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2600679&req=5

fig1: Paraformaldehyde-fixed, paraffin-embedded and haematoxylin–eosin stained thyroid tissues from C57Bl/6, E7 and RET/PTC3. (A–C) 2, 6, and 10-month C57Bl/6 thyroids respectively; (D–F) 2-, 6-, 10-month E7 thyroids respectively; (G–I) 2-, 6-, 10-month RET/PTC3 respectively, (I) two lobes from the same mouse; (J and K) 2-, and 6-month RET/PTC3 with remodeling and cyst (diffuse sclerosing); upper right insert of J: macrophages infiltration, middle right insert of J: nuclear inclusion; low right insert of J: thick spindle-like cells in between follicles. Original magnification 2.5 × . Scale bar: 1 mm.
Mentions: At 2 months, WT mouse thyroids harboured cuboidal follicular cells lining small follicles (Figures 1A–C and 2A). The size of the follicles became heterogeneous at 6 months, with dominant large follicles lined by flat cells at 10 months (Figure 2B and C).

Bottom Line: There is an 'oncogene dependent' cellular signature, maintained at all studied ages in the E7 model, less in the RET/PTC3 model.The Tg-E7 model was less heterogeneous, with a dominant goitrous pattern.The solid tumour already described in the RET/PTC3 models associated with cribriform patterns, suggested 'PTC spindle cell changes' as in humans PTC rather than the equivalent of the solid human PTC.

View Article: PubMed Central - PubMed

Affiliation: Institut de Recherche Interdisciplinaire (IRIBHM), Faculté de Médecine, Université Libre de Bruxelles (ULB), Campus Erasme, Route de Lennik 808, B 1070 Bruxelles, Belgique. lingjin@ulb.ac.be

ABSTRACT
Human rearranged RET/PTC3 (papillary thyroid carcinoma) proto-oncogene and high-risk human papillomavirus (HPV) type 16 E7 oncogene induces in the mouse a neoplastic transformation of thyroid follicular cells. We present a detailed immuno-histological study (170 mouse thyroids: RET/PTC3, E7, wild type, 2- to 10-month-old) with cell cycle proliferation and signalling pathway indicators. The characteristics of both models are different. There is an 'oncogene dependent' cellular signature, maintained at all studied ages in the E7 model, less in the RET/PTC3 model. During tumour development a large heterogeneity occurred in the Tg-RET/PTC3 model within a same tumour or within a same thyroid lobe. The Tg-E7 model was less heterogeneous, with a dominant goitrous pattern. The solid tumour already described in the RET/PTC3 models associated with cribriform patterns, suggested 'PTC spindle cell changes' as in humans PTC rather than the equivalent of the solid human PTC. Proliferation and apoptosis in the two thyroid models are related to the causal oncogene rather than reflect a general tumorigenic process. The thyroids of RET/PTC3 mice appeared as a partial and transient model of human PTCs, whereas the Tg-E7 mice do not belong to the usual PTC type.

Show MeSH
Related in: MedlinePlus